Particle characterisation in drug delivery

The use of materials in nano-scale dimensions is proving to be a promising approach to overcome drug delivery challenges. ‘Nanomedicine’ technologies are gradually achieving commercial success and reaching the clinic. Sub-micron nanocarriers have the potential to ferry the therapeutic to its site of action and in this process overcome the biological barriers and achieve targeted drug delivery, controlled or stimuli-responsive delivery and protect the therapeutic from biological milieus. Many different types of nanocarriers have been described, including polymeric nanoparticles (NPs), liposomes, solid lipid NPs, micelles, dendrimers and metal NPs among other systems (the terms ‘nanomedicine’, ‘NP’ and ‘nanocarriers’ are used herein to describe all nanosystems). Of particular interest are nanocarriers with the ability to act selectively and target cell internalisation processes, guiding the therapeutic into subcellular regions. NP features important in dictating their drug delivery performance, including targeted delivery and cellular trafficking, are their size, shape and surface characteristics such as surface charge, chemistry and the distribution of ligands

Bridging Single-Particle Characterisation Gaps of Optical Microscopy in the Nano-Submicron Regime

As the practical importance of particles in the nano-submicron size regime continues to increase in both biomedical applications and industrial processes, so does the need for accurate and versatile characterisation methods. Optical scattering microscopy methods are commonly used for single-particle characterisation as they provide quick measurements at physiologically relevant conditions with detection limits reaching down to individual biomolecules. However, quantitative particle characterisation using optical microscopy often rely on assumptions about the surrounding media and theparticle, including solution viscosity, boundary conditions, as well as particle shape and material. Since these assumptions are difficult to evaluate, particle characterisation beyond hydrodynamic radius and/or mass remains challenging.The aim of this thesis is to contribute to bridging the gaps that limit quantitative optical microscopy-based characterisation of individual particles in the nano-submicron regime by both developing new and improving existing microscopy methods. Specifically, in Paper I a method was developed to evaluate the relation between diffusivity and particle size to enable measurements of the hydrodynamic boundary condition. Papers II-V are based around the development of holographic nanoparticle tracking (H-NTA) and extensions thereof, with the intent of using the complex-valued optical field for material sensitive particle characterisation with minimal dependence on the surrounding media. In Paper II, H-NTA by itself was used to characterise suspensions containing nanobubbles and molecular aggregates. In Paper III, the combination of H-NTA with deep learning was used to achieve simultaneous quantification of size and refractive index directly from single microscopy images, which allowed detection of reversible fluctuations in nanoparticle aggregates. In Paper IV, H-NTA augmented with a low frequency attenuation filter, coined twilight holography, was used to investigate the interaction between herpes viruses and functionalised gold nanoparticles in terms of size, bound gold mass, and virus refractive index. In Paper V, the combination of twilight holography and interferometric scattering microscopy (iSCAT) was used to quantify both size and polarizability of individual nanoparticles without the need of detailed knowledge about the surrounding media. Taken together, the presented results in this thesis provide both new insights into heterogenous nanoparticle systems and contributes to narrowing the gap for detailed optical particle characterisation

Lower Hunter particle characterisation study 4th progress report (Summer)

The Lower Hunter Particle Characterisation Study was commissioned by the NSW Environment Protection Authority in 2013 to investigate the composition and major sources of particle pollution in the Lower Hunter. The study was conducted by scientists from the former Office of Environment and Heritage (OEH), CSIRO and the Australian Nuclear Science and Technology Organisation (ANSTO), with oversight from the NSW Ministry of Health, and completed in 2016. Focusing on very small particles, invisible to the human eye, which can be inhaled and can pass through the throat and nose and into the lungs, the study aimed to determine the composition and major sources of fine particles (PM2.5) and coarse particles (PM2.5-10). Fine particles were monitored at four sites, including two sites representative of regional population exposures (Newcastle, Beresfield) and two sites near the Port of Newcastle (Mayfield and Stockton). Coarse particles were monitored at Mayfield and Stockton, the two sites near the Port of Newcastle

Lower Hunter particle characterisation study 2nd progress report (Winter).

The Lower Hunter Particle Characterisation Study was commissioned by the NSW Environment Protection Authority in 2013 to investigate the composition and major sources of particle pollution in the Lower Hunter. The study was conducted by scientists from the former Office of Environment and Heritage (OEH), CSIRO and the Australian Nuclear Science and Technology Organisation (ANSTO), with oversight from the NSW Ministry of Health, and completed in 2016. Focusing on very small particles, invisible to the human eye, which can be inhaled and can pass through the throat and nose and into the lungs, the study aimed to determine the composition and major sources of fine particles (PM2.5) and coarse particles (PM2.5-10). Fine particles were monitored at four sites, including two sites representative of regional population exposures (Newcastle, Beresfield) and two sites near the Port of Newcastle (Mayfield and Stockton). Coarse particles were monitored at Mayfield and Stockton, the two sites near the Port of Newcastle

An optimal nephelometric model design method for particle characterisation

Scattering nephelometry is a particle characterisation method applicable to fluid suspensions containing impurities. Solutions derived by the method feature particle classification by size (diameter), volume or texture as well as continuous on-line and in-situ monitoring, The replacement of turbidimeters with nephelometers in many existing turbidity applications could result in suppression of side effects caused by limitations and uncontrolled parameter drifts and satisfaction of problem-defined constraints at virtually no change in implementation cost. A major issue of nephelometric model design is the selection of a mathematical tool suitable for the modelling of the data analysis system. [Continues.

Particle characterisation of rail sands for understanding tribological behaviour

Low adhesion between a train’s wheel and the rail can cause performance and safety issues, costing the UK rail industry ~£345 m/annum. Sand is applied to the wheel/rail interface to increase traction when low adhesion conditions are present. In order to improve performance, an understanding of how particles are entrained into and act within the interface is needed. This paper outlines a particle characterisation framework and applies it to sands used in the rail industry: Leighton Buzzard (LB), Central European (CE), and Derbyshire Youlgreave (DY) sand. The largest difference found in this framework was between the sand’s particle size, LB being largest, then CE, then DY. A high pressure torsion rig measured traction when the sands were applied to dry, wet, and leaf extract contaminated conditions, the latter two representing low adhesion conditions. All sands had no impact on wheel/rail adhesion in dry conditions; in low adhesion conditions DY had little influence, whereas LB and CE were found to increase traction. Particles in dry conditions had no effect on test specimen surface roughness, whereas roughness increased when sand was applied in low adhesion conditions. The developed characterisation framework provides a platform for assessing prospective adhesion enhancing particles

Prethermalisation and the Build Up of the Higgs Effect

Real time field excitations in the broken symmetry phase of the classical abelian Gauge+Higgs model are studied numerically in the unitary gauge, for systems starting from the unstable maximum of the Higgs potential.Comment: 5 pages, 6 figures, to appear in proceedings of SEWM'0

Measurements of the scattering characteristics of sediment suspensions with different mineralogical compositions

Acoustic studies of suspended sediments often assume the dominant mineral in suspension is quartz, the density and intrinsic scattering properties of which are implemented when inverting acoustic backscatter data collected at sea. However, compositional analysis studies of suspended and sea-bed particulate material show a wide range of mineral species contribute to the inorganic fraction of sediments in the marine environment. Whilst no theoretical framework exists to predict the acoustic properties of irregularly shaped sediment grains, the density, compressional, and shear wave velocities of common marine mineral species can vary by up to a factor of two. In this study, we present and compare measurements of the intrinsic scattering parameters, namely the normalized total scattering cross section, χ, and the backscatter form function, f, obtained from homogenous suspensions of irregularly shaped sand sized grains of both magnetite and quartz. Our preliminary measurements suggest that in the geometric scattering regime, χ is enhanced for magnetite sands by ~ 100 % relative to quartz. Similarly, measurements of the form function for magnetite sands are enhanced by ~ 33 % relative to quartz in the geometric regime, though no measurable difference was observed in the Rayleigh regime. The implications of these results for acoustic backscatter data collected at sea are discussed