Colloidal drug probe : method development and validation for adhesion force measurement using atomic force microscopy

This study demonstrates a novel technique of preparing drug colloid probes to determine the adhesion force between the drug salbutamol sulphate (SS) and the surfaces of polymer microparticles to be used as carriers for the dispersion of drug particles from a dry powder inhaler (DPI) formulation. Initially model silica probes of approximately 4 μm size, similar to a drug particle used in DPI formulations, were coated with a saturated SS solution with the aid of capillary forces acting between the silica probe and the drug solution. The developed method of ensuring a smooth and uniform layer of SS on the silica probe was validated using X-Ray Photoelectron Spectroscopy (XPS) and Scanning Electron Microscopy (SEM). Using the same technique, silica microspheres preattached on the AFM cantilever were coated with SS. The adhesion forces between the silica probe and drug coated silica (drug probe) and polymer surfaces (hydrophilic and hydrophobic) were determined. Our experimental results showed that the technique for preparing the drug probe was robust and can be used to determine the adhesion force between hydrophilic/hydrophobic drug probe and carrier surfaces to gain a better understanding on drug carrier adhesion forces in DPI formulations.

Colloidal drug probe : Method development and validation for adhesion force measurement using Atomic Force Microscopy

This study demonstrates a novel technique of preparing drug colloid probes to determine the adhesion force between a model drug salbutamol sulphate (SS) and the surfaces of polymer microparticles to be used as carriers for the dispersion of drug particles from dry powder inhaler (DPI) formulations. Model silica probes of approximately 4 lm size, similar to a drug particle used in DPI formulations, were coated with a saturated SS solution with the aid of capillary forces acting between the silica probe and the drug solution. The developed method of ensuring a smooth and uniform layer of SS on the silica probe was validated using X-ray Photoelectron Spectroscopy (XPS) and Scanning Electron Microscopy (SEM). Using the same technique, silica microspheres pre-attached on the AFM cantilever were coated with SS. The adhesion forces between the silica probe and drug coated silica (drug probe) and polymer surfaces (hydrophilic and hydrophobic) were determined. Our experimental results showed that the technique for preparing the drug probe was robust and can be used to determine the adhesion force between hydrophilic/ hydrophobic drug probe and carrier surfaces to gain a better understanding on drug carrier adhesion forces in DPI formulations.

Development of optimal designs of insulated rail joints

Proper functioning of Insulated Rail Joints (IRJs) is essential for the safe operation of the railway signalling systems and broken rail identification circuitries. The Conventional IRJ (CIRJ) resembles structural butt joints consisting of two pieces of rails connected together through two joint bars on either side of their web and the assembly is held together through pre-tensioned bolts. As the IRJs should maintain electrical insulation between the two rails, a gap between the rail ends must be retained at all times and all metal contacting surfaces should be electrically isolated from each other using non-conductive material. At the gap, the rail ends lose longitudinal continuity and hence the vertical sections of the rail ends are often severely damaged, especially at the railhead, due to the passage of wheels compared to other continuously welded rail sections. Fundamentally, the reason for the severe damage can be related to the singularities of the wheel-rail contact pressure and the railhead stress. No new generation designs that have emerged in the market to date have focussed on this fundamental; they only have provided attention to either the higher strength materials or the thickness of the sections of various components of the IRJs. In this thesis a novel method of shape optimisation of the railhead is developed to eliminate the pressure and stress singularities through changes to the original sharp corner shaped railhead into an arc profile in the longitudinal direction. The optimal shape of the longitudinal railhead profile has been determined using three nongradient methods in search of accuracy and efficiency: (1) Grid Search Method; (2) Genetic Algorithm Method and (3) Hybrid Genetic Algorithm Method. All these methods have been coupled with a parametric finite element formulation for the evaluation of the objective function for each iteration or generation depending on the search algorithm employed. The optimal shape derived from these optimisation methods is termed as Stress Minimised Railhead (SMRH) in this thesis. This optimal SMRH design has exhibited significantly reduced stress concentration that remains well below the yield strength of the head hardened rail steels and has shifted the stress concentration location away from the critical zone of the railhead end. The reduction in the magnitude and the relocation of the stress concentration in the SMRH design has been validated through a full scale wheel – railhead interaction test rig; Railhead strains under the loaded wheels have been recorded using a non-contact digital image correlation method. Experimental study has confirmed the accuracy of the numerical predications. Although the SMRH shaped IRJs eliminate stress singularities, they can still fail due to joint bar or bolt hole cracking; therefore, another conceptual design, termed as Embedded IRJ (EIRJ) in this thesis, with no joint bars and pre-tensioned bolts has been developed using a multi-objective optimisation formulation based on the coupled genetic algorithm – parametric finite element method. To achieve the required structural stiffness for the safe passage of the loaded wheels, the rails were embedded into the concrete of the post tensioned sleepers; the optimal solutions for the design of the EIRJ is shown to simplify the design through the elimination of the complex interactions and failure modes of the various structural components of the CIRJ. The practical applicability of the optimal shapes SMRH and EIRJ is demonstrated through two illustrative examples, termed as improved designs (IMD1 & IMD2) in this thesis; IMD1 is a combination of the CIRJ and the SMRH designs, whilst IMD2 is a combination of the EIRJ and SMRH designs. These two improved designs have been simulated for two key operating (speed and wagon load) and design (wheel diameter) parameters that affect the wheel-rail contact; the effect of these parameters has been found to be negligible to the performance of the two improved designs and the improved designs are in turn found far superior to the current designs of the CIRJs in terms of stress singularities and deformation under the passage of the loaded wheels. Therefore, these improved designs are expected to provide longer service life in relation to the CIRJs.

A novel identification method for ultra trace detection of biomolecules using functionalised Surface Enhanced Raman Spectroscopy (SERS)

This thesis developed a new method for measuring extremely low amounts of organic and biological molecules, using Surface enhanced Raman Spectroscopy. This method has many potential applications, e.g. medical diagnosis, public health, food provenance, antidoping, forensics and homeland security. The method development used caffeine as the small molecule example, and erythropoietin (EPO) as the large molecule. This method is much more sensitive and specific than currently used methods; rapid, simple and cost effective. The method can be used to detect target molecules in beverages and biological fluids without the usual preparation steps.

A novel fully validated LC–MS/MS method for quantification of pyridoxal-5′-phosphate concentrations in samples of human whole blood

Quantification of pyridoxal-5´-phosphate (PLP) in biological samples is challenging due to the presence of endogenous PLP in matrices used for preparation of calibrators and quality control samples (QCs). Hence, we have developed an LC-MS/MS method for accurate and precise measurement of the concentrations of PLP in samples (20 µL) of human whole blood that addresses this issue by using a surrogate matrix and minimizing the matrix effect. We used a surrogate matrix comprising 2% bovine serum albumin (BSA) in phosphate buffer saline (PBS) for making calibrators, QCs and the concentrations were adjusted to include the endogenous PLP concentrations in the surrogate matrix according to the method of standard addition. PLP was separated from the other components of the sample matrix using protein precipitation with trichloroacetic acid 10% w/v. After centrifugation, supernatant were injected directly into the LC-MS/MS system. Calibration curves were linear and recovery was > 92%. QCs were accurate, precise, stable for four freeze-thaw cycles, and following storage at room temperature for 17h or at -80 °C for 3 months. There was no significant matrix effect using 9 different individual human blood samples. Our novel LC-MS/MS method has satisfied all of the criteria specified in the 2012 EMEA guideline on bioanalytical method validation.

Development of a method to measure upper eyelid pressure on the cornea

Purpose: The cornea is known to be susceptible to forces exerted by eyelids. There have been previous attempts to quantify eyelid pressure but the reliability of the results is unclear. The purpose of this study was to develop a technique using piezoresistive pressure sensors to measure upper eyelid pressure on the cornea. Methods: The technique was based on the use of thin (0.18 mm) tactile piezoresistive pressure sensors, which generate a signal related to the applied pressure. A range of factors that influence the response of this pressure sensor were investigated along with the optimal method of placing the sensor in the eye. Results: Curvature of the pressure sensor was found to impart force, so the sensor needed to remain flat during measurements. A large rigid contact lens was designed to have a flat region to which the sensor was attached. To stabilise the contact lens during measurement, an apparatus was designed to hold and position the sensor and contact lens combination on the eye. A calibration system was designed to apply even pressure to the sensor when attached to the contact lens, so the raw digital output could be converted to actual pressure units. Conclusions: Several novel procedures were developed to use tactile sensors to measure eyelid pressure. The quantification of eyelid pressure has a number of applications including eyelid reconstructive surgery and the design of soft and rigid contact lenses.

Towards a unified method for the knowledge based urban development framework

Purpose–The growing debate in the literature indicates that the initiative to implement Knowledge Based Urban Development (KBUD) approaches in urban development process is neither simple nor quick. Many research efforts has therefore, been put forward to the development of appropriate KBUD framework and KBUD practical approaches. But this has lead to a fragmented and incoherent methodological approach. This paper outlines and compares a few most popular KBUD frameworks selected from the literature. It aims to identify some key and common features in the effort to achieve a unified method of KBUD framework. Design/methodology/approach–This paper reviews, examines and identifies various popular KBUD frameworks discussed in the literature from urban planners’ viewpoint. It employs a content analysis technique i.e. a research tool used to determine the presence of certain words or concepts within texts or sets of texts. Originality/value–The paper reports on the key and common features of a few selected most popular KBUD frameworks. The synthesis of the results is based from a perspective of urban planners. The findings which encompass a new KBUD framework incorporating the key and common features will be valuable in setting a platform to achieve a unified method of KBUD. Practical implications –The discussion and results presented in this paper should be significant to researchers and practitioners and to any cities and countries that are aiming for KBUD. Keywords – Knowledge based urban development, Knowledge based urban development framework, Urban development and knowledge economy

Development of the response coefficient-root function method for the transient vibration serviceability design of flat concrete floors

The vibration serviceability limit state is an important design consideration for two-way, suspended concrete floors that is not always well understood by many practicing structural engineers. Although the field of floor vibration has been extensively developed, at present there are no convenient design tools that deal with this problem. Results from this research have enabled the development of a much-needed, new method for assessing the vibration serviceability of flat, suspended concrete floors in buildings. This new method has been named, the Response Coefficient-Root Function (RCRF) method. Full-scale, laboratory tests have been conducted on a post-tensioned floor specimen at Queensland University of Technology’s structural laboratory. Special support brackets were fabricated to perform as frictionless, pinned connections at the corners of the specimen. A series of static and dynamic tests were performed in the laboratory to obtain basic material and dynamic properties of the specimen. Finite-element-models have been calibrated against data collected from laboratory experiments. Computational finite-element-analysis has been extended to investigate a variety of floor configurations. Field measurements of floors in existing buildings are in good agreement with computational studies. Results from this parametric investigation have led to the development of new approach for predicting the design frequencies and accelerations of flat, concrete floor structures. The RCRF method is convenient tool to assist structural engineers in the design for the vibration serviceability limit-state of in-situ concrete floor systems.

Knowledge sharing leveraging new product development activities to derive enhanced business performance : mixed method study

Knowledge has been widely recognised as a determinant of business performance. Business capabilities require an effective share of resource and knowledge. Specifically, knowledge sharing (KS) between different companies and departments can improve manufacturing processes since intangible knowledge plays an enssential role in achieving competitive advantage. This paper presents a mixed method research study into the impact of KS on the effectiveness of new product development (NPD) in achieving desired business performance (BP). Firstly, an empirical study utilising moderated regression analysis was conducted to test whether and to what extent KS has leveraging power on the relationship between NPD and BP constructs and variables. Secondly, this empirically verified hypothesis was validated through explanatory case studies involving two Taiwanese manufacturing companies using a qualitative interaction term pattern matching technique. The study provides evidence that knowledge sharing and management activities are essential for deriving competitive advantage in the manufacturing industry.

The development of a new method for the determination of concentrations of carbonaceous gases using a non-dispersive infrared sensor

An analytical method for the detection of carbonaceous gases by a non-dispersive infrared sensor (NDIR) has been developed. The calibration plots of six carbonaceous gases including CO2, CH4, CO, C2H2, C2H4 and C2H6 were obtained and the reproducibility determined to verify the feasibility of this gas monitoring method. The results prove that squared correlation coefficients for the six gas measurements are greater than 0.999. The reproducibility is excellent, thus indicating that this analytical method is useful to determinate the concentrations of carbonaceous gases.

Development of a simplified design method to predict the fire rating of LSF walls

Recent fire research into the behaviour of light gauge steel frame (LSF) wall systems has devel-oped fire design rules based on Australian and European cold-formed steel design standards, AS/NZS 4600 and Eurocode 3 Part 1.3. However, these design rules are complex since the LSF wall studs are subjected to non-uniform elevated temperature distributions when the walls are exposed to fire from one side. Therefore this paper proposes an alternative design method for routine predictions of fire resistance rating of LSF walls. In this method, suitable equations are recommended first to predict the idealised stud time-temperature pro-files of eight different LSF wall configurations subject to standard fire conditions based on full scale fire test results. A new set of equations was then proposed to find the critical hot flange (failure) temperature for a giv-en load ratio for the same LSF wall configurations with varying steel grades and thickness. These equations were developed based on detailed finite element analyses that predicted the axial compression capacities and failure times of LSF wall studs subject to non-uniform temperature distributions with varying steel grades and thicknesses. This paper proposes a simple design method in which the two sets of equations developed for time-temperature profiles and critical hot flange temperatures are used to find the failure times of LSF walls. The proposed method was verified by comparing its predictions with the results from full scale fire tests and finite element analyses. This paper presents the details of this study including the finite element models of LSF wall studs, the results from relevant fire tests and finite element analyses, and the proposed equations.

Development of a rapid and validated method for investigating the metabolism of scoparone in rat using ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry

Scoparone (6,7-dimethoxycoumarin) is known to have a wide range of pharmacological properties. In this study, a rapid and validated ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry (UPLC/ESI-QTof-MS) method was developed to investigate the metabolism of scoparone in rat for the first time. The new method reduced the sample handling and analytical time by three- to six-fold, and the detection limit by five- to 1000-fold, compared to published methods. Far more metabolites were detected and identified compared to published data, which were preliminarily identified as scopoletin, isoscopoletin, isofraxidin, and fraxidin, respectively, when subjected to tandem mass spectrometry analyses. It is found that the metabolic trajectory of scoparone in rat focused on phase I metabolism which is obviously different from published results, and revealed a wide range of pharmacological properties of scoparone partly attributed to the bioactivities of its metabolites.

Development and validation of a ultra performance LC-ESI/MS method for analysis of metabolic phenotypes of healthy men in day and night urine samples

Ultra-performance LC coupled to quadrupole TOF/MS (UPLC-QTOF/MS) in positive and negative ESI was developed and validated to analyze metabolite profiles for urine from healthy men during the day and at night. Data analysis using principal components analysis (PCA) revealed differences between metabolic phenotypes of urine in healthy men during the day and at night. Positive ions with mass-to-charge ratio (m/z) 310.24 (5.35 min), 286.24 (4.74 min) and 310.24 (5.63 min) were elevated in the urine from healthy men at night compared to that during the day. Negative ions elevated in day urine samples of healthy men included m/z 167.02 (0.66 min), 263.12 (2.55 min) and 191.03 (0.73 min), whilst ions m/z 212.01 (4.77 min) were at a lower concentration in urine of healthy men during the day compared to that at night. The ions m/z 212.01 (4.77 min), 191.03 (0.73 min) and 310.24 (5.35 min) preliminarily correspond to indoxyl sulfate, citric acid and N-acetylneuraminic acid, providing further support for an involvement of phenotypic difference in urine of healthy men in day and night samples, which may be associated with notably different activities of gut microbiota, velocity of tricarboxylic acid cycle and activity of sialic acid biosynthesis in healthy men as regulated by circadian rhythm of the mammalian bioclock.