P. Rhodri Williams

A study of microstructural templating in fibrin–thrombin gel networks by spectral and viscoelastic analysis

We report a study of the microstructural templating role of incipient fibrin–thrombin gels by analysis of rheological and confocal microscope measurements. Fractal analysis based on the spectral dimension is used, for the first time, to characterise fibrin gel microstructure in terms of the internal connectivity of gel networks. A significant correlation is found between the fractal characteristics of the incipient gel network and its eventual mature form, confirming that incipient gel microstructure templates ensuing gel development. We report an analytical basis for the study of this templating effect which reveals two different regimes of microstructural development. The first involves low thrombin concentration, in which increasing concentration decreases the gel formation time and alters the fractal characteristics of both incipient and mature gels. In the second regime, involving higher thrombin concentrations, the incipient gel formation time and the fractal characteristics of incipient and mature gels show little variation. The network formation is discussed in terms of computer simulations of incipient fractal networks by the activation-limited aggregation of clusters of rod-like particles. The significance of the work is discussed in terms of biomaterials design for applications involving controlled drug release and wound healing, and improved predictions of blood clot susceptibility to lysis.

Application of atomic force microscopy to the study of natural and model soil particles

The structure and surface chemistry of soil particles has extensive impact on many bulk scale properties and processes of soil systems and consequently the environments that they support. There are a number of physiochemical mechanisms that operate at the nanoscale which affect the soils capability to maintain native vegetation and crops; this includes soil hydrophobicity and the soils capacity to hold water and nutrients. The present study used atomic force microscopy in a novel approach to provide unique insight into the nanoscale properties of natural soil particles that control the physiochemical interaction of material within the soil column. There have been few atomic force microscopy studies of soil, perhaps a reflection of the heterogeneous nature of the system. The present study adopted an imaging and force measurement research strategy that accounted for the heterogeneity and used model systems to aid interpretation. The surface roughness of natural soil particles increased with depth in the soil column a consequence of the attachment of organic material within the crevices of the soil particles. The roughness root mean square calculated from ten 25 μm2 images for five different soil particles from a Netherlands soil was 53.0 nm, 68.0 nm, 92.2 nm and 106.4 nm for the respective soil depths of 0–10 cm, 10–20 cm, 20–30 cm and 30–40 cm. A novel analysis method of atomic force microscopy phase images based on phase angle distribution across a surface was used to interpret the nanoscale distribution of organic material attached to natural and model soil particles. Phase angle distributions obtained from phase images of model surfaces were found to be bimodal, indicating multiple layers of material, which changed with the concentration of adsorbed humic acid. Phase angle distributions obtained from phase images of natural soil particles indicated a trend of decreasing surface coverage with increasing depth in the soil column. This was consistent with previous macroscopic determination of the proportions of organic material chemically extracted from bulk samples of the soils from which specimen particles were drawn. Interaction forces were measured between atomic force microscopy cantilever tips (Si3N4) and natural soil and model surfaces. Adhesion forces at humic acid free specimen surfaces (Av. 20.0 nN), which are primarily hydrophilic and whose interactions are subject to a significant contribution from the capillary forces, were found to be larger than those of specimen surfaces with adsorbed humic acid (Av. 6.5 nN). This suggests that adsorbed humic acid increased surface hydrophobicity. The magnitude and distribution of adhesion forces between atomic force microscopy tips and the natural particle surfaces was affected by both local surface roughness and the presence of adsorbed organic material. The present study has correlated nanoscale measurements with established macroscale methods of soil study. Thus, the research demonstrates that atomic force microscopy is an important addition to soil science that permits a multiscale analysis of the multifactorial phenomena of soil hydrophobicity and wetting.

Studies of cavitation and ice nucleation in ‘doubly-metastable’ water: time-lapse photography and neutron diffraction

High-speed photographic studies and neutron diffraction measurements have been made of water under tension in a Berthelot tube. Liquid water was cooled below the normal ice-nucleation temperature and was in a doubly-metastable state prior to a collapse of the liquid state. This transition was accompanied by an exothermic heat release corresponding with the rapid production of a solid phase nucleated by cavitation. Photographic techniques have been used to observe the phase transition over short time scales in which a solidification front is observed to propagate through the sample. Significantly, other images at a shorter time interval reveal the prior formation of cavitation bubbles at the beginning of the process. The ice-nucleation process is explained in terms of a mechanism involving hydrodynamically-induced changes in tension in supercooled water in the near vicinity of an expanding cavitation bubble. Previous explanations have attributed the nucleation of the solid phase to the production of high positive pressures. Corresponding results are presented which show the initial neutron diffraction pattern after ice-nucleation. The observed pattern does not exhibit the usual crystalline pattern of hexagonal ice [I(h)] that is formed under ambient conditions, but indicates the presence of other ice forms. The composite features can be attributed to a mixture of amorphous ice, ice-I(h)/I(c) and the high-pressure form, ice-III, and the diffraction pattern continues to evolve over a time period of about an hour.

Validation of fractal dimension of the incipient blood clot in ST-segment-elevation myocardial infarction

Abstract Background More than 200 combinations of antiplatelet and anticoagulant drugs can be given during an acute cardiac event. However, no biomarker is available to assess their global effect on clot formation and structure. Fractal dimension (D f ) and clot formation time (T GP ) are global markers of haemostasis that have been validated in healthy and anticoagulated blood. In contrast to standard coagulation assays, these biomarkers use unadulterated whole blood and are measured immediately at the bedside. D f quantifies clot microstructure whereas T GP is a real-time measure of clotting time, and both are calculated from the gel point (GP). We aimed to validate D f and T GP in ST-segment-elevation myocardial infarction (STEMI) and assess the effect of therapeutic intervention. Methods We recruited prospectively patients with STEMI undergoing primary percutaneous coronary intervention (PCI). Venous blood samples were collected on admission (after 300 mg of aspirin), after PCI (after clopidogrel, heparin, and bivalirudin), and 24 h after admission. In addition to assessment of D f and T GP , each sample was assessed by standard coagulation tests and a full blood count. Wilcoxon signed-rank and paired t tests were used to compare changes from admission to after PCI and at 24 h. Spearmans correlation analysis was done to explore any associations. Normality was assessed with the Shapiro-Wilks test. This study was approved by the local Research Ethics Committee (REC Number 07/WMW02/34) and written informed consent was obtained from all participants. Findings 33 patients (mean age 69 years [SD 12]; 19 men, 14 women) were included. D f on admission (mean 1·75, SD 0·05) was higher than values we have previously reported in healthy individuals despite use of antiplatelet therapy. D f after PCI was significantly lower than D f on admission (mean 1·64 [SD 0·06] vs 1·75 [0·05], p f at 24 h was similar to that on admission. T GP was significantly prolonged at after-PCI measurement compared with admission (median 723 s [IQR 492–1793] vs 210 [173–314], p f correlated negatively with T GP ( r =−0·75, p r =−0·49, p r =−0·52, p r =0·36, p=0·0009). There was no significant correlation observed between D f and platelets or haematocrit. Interpretation Therapeutic manipulation in STEMI especially with drugs given during PCI had a striking effect on clot structure and rate of coagulation as measured by D f and T GP . Larger studies are in progress to evaluate potential therapeutic strategies based on these biomarkers and their accuracy in detecting hypocoagulable and hypercoagulable states, and predicting cardiovascular risk. Funding National Institute for Social Care and Health Research, Engineering and Physical Sciences Research Council.

Chapter 9 – Application of Atomic Force Microscopy for the Study of Tensile and Microrheological Properties of Fluids

Publisher Summary This chapter explains the application of atomic force microscopy (AFM) for the study of tensile and microrheological properties of fluids. AFM is one of the most successful techniques for the characterization of surfaces and is routinely used to describe structural details with nanoscale resolution. The ability of AFM to differentiate between local mechanical properties is well known. The atomic force microscope is clearly a powerful tool for the investigation of forces which govern the mechanics of processes occurring at or below the microscale, and the exceptional ability of atomic force microscopy to determine forces associated with the microscope deformation and flow of fluids is discussed. An understanding of the rheology of complex fluids is of fundamental importance in many practical engineering and biomedical applications. The rheological behavior of thin liquid films is an important aspect of lubrication and printing—processes that often involve mesoscale thickness films undergoing rapid deformation between separating surfaces. The nanorheological properties of polymeric liquids can be obtained by adapting techniques such as an surface force apparatus (SFA) or an AFM to act in a dynamic mode. However, the results of AFM studies are often more difficult to interpret than those derived from SFA experiments due to uncertainties about the zero separation distance, the influence of probe asperities, and torsional deflections.

Rheometrical studies of blood clot formation by oscillatory shear, thromboelastography, sonoclot analysis and free oscillation rheometry

We report studies of the coagulation of samples of whole human blood by oscillatory shear techniques, including Fourier Transform Mechanical Spectroscopy (FTMS). These techniques are used herein to identify the Gel Point of coagulating blood in terms of the Chambon‐Winter Gel Point criterion which provides a rheometrical basis for detecting the establishment of an incipient clot. A comparison of the results of FTMS with those obtained from measurements involving a Thromboelastograph (TEG), a Sonoclot Analyzer and a Free Oscillation Rheometer (FOR) indicate that the latter techniques are not capable of detecting the incipient clot, whose establishment occurs several minutes prior to TEG or FOR‐based assessments of clot formation time. The results of the present study suggest that FTMS is a useful tool in blood clotting research, being capable of providing a global coagulation profile in addition to detecting the instant of incipient clot formation.

The Effects of Stressing Rate on Measurements of the Cavitation Threshold of Monograde Lubricants by Pulses of Tension

This paper reports the results of experiments in which samples of degassed monograde lubricants, namely 10 W and 40 Diesel motor oils, are subjected to dynamic stressing by pulses of tension. The pulse reflection technique employed allows the rate of development of tension in the liquid to be varied in a systematic manner, in order to investigate its influence on the resulting measurement of the liquids cavitation threshold (or ‘effective’ tensile strength), Fc. Results are reported for experiments involving a range of stressing rates, from 0.6 bar/μs to 1.4 bar/μs for monograde 10 W and 40 Diesel motor oils over the temperature range 25 °C<T<110 °C. These experiments, which are the first of their kind to be reported, indicate that, at any given temperature, Fc increases with increasing stressing rate (156 bar<Fc<228 bar at 25 °C and, 130 bar<Fc<156 bar at 110 °C for the 10 W oil and 155 bar<Fc<223 bar at 25 °C and, 124 bar<Fc<177 bar at 110 °C for the 40 Diesel oil). These results provide evidence to su...

Break-up in Capillary Thinning Experiments: Using the CaBER to Determine Maximum Tensile Strength at Low Stressing Rates

The maximum tensile strength of fluids is an important guide to the onset of cavitation. Being able to predict the onset of cavitation is important in formulation for industries as diverse as printing and automotive industries. A technique has been developed to use break‐up at the end of a capillary thinning experiment to determine the maximum tensile strength of the test fluid. The technique has been applied to a range of concentrations and molecular weights of polyethylene glycol. The results have been validated by comparison with the values and behaviours observed from the bullet piston apparatus. Some discussion regarding the advantages, differences and applicability of using the CaBER is also provided. Some discussion is also provided regarding break‐up in capillary thinning experiments.

The Tensile Strength of Water as a Function of Temperature

This paper reports the results of measurements of the effective tensile strength Fc of water, in experiments involving a pulse of tension (‘negative pressure’) created by the reflection of a pressure pulse at a boundary, as a function of temperature. Using a modified ‘Bullet-Piston’ (B-P) pulse reflection apparatus, measurements presented herein show that degassed, deionised water is capable of sustaining tensions an order of magnitude greater than previously reported in B-P work. A theoretical explanation is developed indicating that the pressure records arising in B-P experiments are the result of cavitation due to a pulse of tension. Results are reported for measurements of Fc made over the temperature range 1°C ≤ T ≤ 95°C.Copyright

Cavitation Phenomena in Thin Films of Newtonian, Non-Newtonian and Viscoelastic Fluids Due to Rapid Bubble Expansion Under Pulses of Negative Pressure

We report studies of the growth of a cavitation bubble in terms of the development of hydrodynamic pressures within the liquid close to the expanding bubble’s surface. The results of this study are discussed in terms of the possible consequences of cavitation bubble expansion in Newtonian and non-Newtonian, shear-thinning fluids (such as synovial fluid). Contrary to previous indications in the literature, non-Newtonian (specifically, shear-thinning) behaviour is found to be significant in this context, insofar as it may result in markedly enhanced tensions due to the pressure waves developed about a growing bubble during the latter stages of its expansion phase. The magnitude of the tensions so developed are compared with estimates of cavitation thresholds (Fc ) which are obtained from experiments involving the reflection of pulsed ultrasound at a flexible boundary. Under some circumstances the tensions developed about the growing cavity are shown to be commensurate with Fc . The possible consequences of these findings are discussed in terms of cavitation damage to blood vessels or other biological tissues.Copyright