Chemical and Biomolecular Engineering - Theses
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ItemSynthesis and characterizations of anticancer amphiphilic star polypeptides( 2017)The cancer had replaced infectious diseases as the second major leading cause of deaths globally in 2013. Currently, chemotherapy is the main treatment option for inoperable and metastatic cancers. Disappointingly, conventional chemotherapy based on DNA disrupting agents are not successful in more than 50% of cases. The main reason behind most failures in chemotherapies is the development of multidrug resistance (MDR) in cancer cells which nullify the actions of all available chemotherapeutic drugs. Therefore, the development of new anticancer drugs based on the novel mode of actions that can bypass MDR is urgently needed. Previous works from our group have established star-structured amphiphilic polypeptides as a new class of highly biocompatible antimicrobial agents effective against MDR bacteria through membrane disrupting actions. Inspired by many natural-occurring membranolytic host defence peptides (HDPs) that display dual antimicrobial and anticancer activities, this thesis sought to extend the therapeutic scope of amphiphilic polypeptides to anticancer applications. A library of linear and star-structured polypeptides consisting varying compositions of lysine, leucine and valine in a random fashion were synthesized via N-carboxyanhydride ring-opening polymerization (NCA ROP). These polypeptides display similar potency in vitro as some HDPs and their synthetic analogues, with IC50 values in the range of 10 – 30 µg/mL toward CT26 mouse colon cancer cells. Moderate selectivity in the range of 1.0 – 3.0 toward CT26 cells over L929 mouse fibroblast cells was observed for the polypeptides. It was found that the architecture of the amphiphilic polypeptides have a predominant influence on their potency, where polypeptides with a greater number of arms have higher potency against both CT26 and L929 cells. On the other hand, polypeptide composition has no significant influence on potency. Studies on the time-kill kinetics of the polypeptides with xCELLigence real-time cell analysis (RTCA) system revealed that each polypeptide has higher killing rates on CT26 cells over L929 cells at the same concentration. It was also observed that helical propensity of the polypeptides show a strong correlation to the initial killing rate of L929 cells but not CT26 cells. In summary, the findings presented in this thesis provided insights on the structure-activity relationships of amphiphilic polypeptides which will aid in the future development and optimization of membranolytic anticancer polypeptides. It is the hope that this thesis will inspire the research community to pursue innovative solutions in the development of future anticancer agents.
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ItemDirected self-assembly of block copolymers and nanostructures( 2017)Self-assembly of block copolymers (BCPs) has attracted considerable attention for decades due to its potential in novel applications. The key to achieve their function critically relies on the control of nanostructure, shape and morphology of the BCP assemblies. The aim of this thesis is to develop a toolbox to manipulate the nanostructure of BCPs in a reliable and predictable manner, and provide mechanistic insights into their self-assembly behaviour. In this work, the strategies used to control the shape and morphology of BCP assemblies lie in three areas: (a) copolymer composition; (b) control of molecular weight distribution; and (c) interfacial properties. In this thesis, a series of BCPs have been synthesised at different compositions and their self-assembled structures have been reported. The influence of the skewed molecular weight distribution and varied dispersity on BCP self-assembly was explored in both solution and thin film systems. The interface between BCP nanoparticles and the surrounding medium was investigated and a morphological evolution from onion-like spheres to axially stacked lamellae has been observed. It is envisaged that the modification of copolymer chemistry and a combination of these addressed strategies will facilitate the synthesis of BCPs assemblies with higher structural complexity.
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ItemCombined shear and compression suspension rheology( 2016)The behaviour of strongly-flocculated suspensions under the combined effect of shear and compression is of significant importance since many of industrial applications combine shear with compressional dewatering to enhance dewatering, such as in raked thickeners and belt filter presses. Determining the constitutive rheological behaviour is required to describe the response of such suspensions to superimposed shear and compressive stresses, however the fragile or soft nature of these suspensions means that multidimensional testing is not straight forward or obvious. The lack of experimental data means that the current understanding of yielding response of flocculated suspensions under combined loadings is unclear. This study focused on testing a model suspension (calcium carbonate flocculated at its isoelectric point) in uniaxial compression using sedimentation and filtration, pure shear using vane rheometry and superimposed shear and compression using a triaxial tester. This last technique is usually used for compacted soils and the application to the rheological analysis of fragile suspensions is novel. Pure shear and uniaxial compressive data across a range of particle sizes and concentrations along with triaxial data for one particle size and volume fraction at various compressive loads and shear rates are presented and analysed. Experimental data shows that the shear and compressive yield stresses exhibit pronounced dependency on particle size and volume fraction in line with expectations based on literature. A triaxial test protocol was developed along with an analysis method, but it was difficult to get good data from the triaxial tester due to slumping. Results showed that calcium carbonate suspension didn’t follow the traditional behaviour seen in soils. In most cases, the shear stress continued to increase with increasing strains and a well-defined peak or constant stress was not reached. The two failure criterions were used to determine the yielding points and results indicated that the failure may have occurred in the range of shear stress, 25-50 kPa and vertical strain, 1-7% according to the first failure criteria. Results indicated that the failure may have occurred in the range of shear stress, 40-90kPa and vertical strain, 5%-10% according to the second failure criteria. The outcome of this study is a test protocol that enables the measurement of suspension constitutive properties under multidimensional loadings.
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ItemInfluence of plate wettability on the performance of a pulsed disc and doughnut column( 2015)The pulsed disc and doughnut column (PDDC) can be seen as a variation of the pulsed perforated plate column (PPPC). It has gained attention due to its simple design, compact nature and lack of internal moving parts leading to safety and economic benefits. The PPPC hydrodynamics and mass transfer performance has been widely studied and reported and due to its similarity, applied to PDDC in a few studies. A few investigators have reported the effect of plate wettability on the performance of PPPC with contradictory results. In this study a tri-n-octylamine – sulphuric acid – water system is used in the study of the hydrodynamics and mass transfer performance of a pilot plant PDDC with mass transfer from dispersed phase to continuous phase and with both aqueous and organic dispersions at low, intermediate and high agitation intensities. To simulate different plate wettability three materials with distinct wetting properties has been selected, namely: Teflon (hydrophobic), Nylon (intermediate) and Stainless Steel (hydrophilic). It was found that Teflon behaves as a super-hydrophobic material in the liquid-liquid system used and may cause phase inversion for organic dispersion with insufficient pulsation. It was found that the magnitude of the effect of agitation intensity on holdup is influenced by the plate wettability. Holdup, measured in terms of characteristic velocity, was lower for Teflon and higher for Stainless Steel for aqueous dispersion. For organic dispersion Nylon showed the lowest characteristic velocity and Stainless Steel the highest. The effect of agitation intensity on the characteristic velocity from the low to intermediate agitation intensity was similar for intermediate and non-wetting plates in both organic and aqueous dispersions, but has a little effect on the wetting plate, i.e. Teflon with dispersed organic and Stainless Steel with dispersed aqueous. Despite the changes in the holdup, the Sauter mean diameter was independent of the plate wettability for dispersed aqueous. However, the distribution of droplet size changed with the operating parameters and three distribution functions were fitted to experimental data, namely: Lognormal, Gamma and Weibull (also known as Rosin-Rammer). The later fitted the raw and grouped data the best. For dispersed organic, the drop size in Nylon plates was significantly smaller than that of Teflon plates. The measured holdup and droplet size was compared with existing models and their accuracy assessed. Two holdup models were modified to incorporate the wetting characteristic of the plate materials. The holdup and droplet size models, suitable for this system, were used to calculate the mass transfer coefficient based on the axial dispersion model which was also compared with existing models and a new correlation developed.
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ItemEngineering of nanostructured polymer and hybrid thin films( 2015)Nanostructured thin film engineering is a versatile method to alter the surface physical properties of a range of materials. Significantly, this altered surface chemistry can modulate the interactions of the material with the external environment, or can be used to introduce novel functionality. Consequently, thin film engineering is of immense fundamental and practical scientific interest, allowing important insight into surface phenomenon, such as lubrication and wetting to be developed. Alternatively, thin film engineering can be used to design materials for optoelectronics and energy transformation, separation or sensing processes, and in the field of biomedical engineering. This thesis aims to study the assembly processes of two thin film fabrication techniques. An understanding of the mechanisms governing film assembly is essential to facilitate design of thin film materials for targeted end applications. Continuous Assembly of Polymers mediated by Atom Transfer Radical Polymerisation (CAP-ATRP) was used to produce thin polymer films, which were characterised by a range of in situ and ex situ techniques. To allow systematic investigation of a range of experimental parameters, synthetic routes to produce CAP-ATRP macrocross-linkers and macroinitiators with tuneable functionality were developed. CAP-ATRP catalyst selection was found to influence film morphology and thickness, and film assembly kinetics. Insight into the initiation process of CAP-ATRP was obtained by varying the structure of the initiator-functionalised surfaces. Low surface areal densities of initiator sites prevented film assembly, likely due to entropic considerations of the adsorbing macrocross-linker chains. Using novel macroinitiators, the effect of initiator spacer length was investigated. Importantly, the addition of flexible spacers between initiator group and macroinitiator backbone increased film growth by CAP-ATRP. Polymer thin film materials are readily complemented by nanostructured metal-organic films, due to the diverse properties introduced by the metal centres. Multimetallic-phenolic network (MMPN) films were assembled by coordination driven self assembly between mixtures of transition metal ions, and the ligand tannic acid (TA). Film assembly was studied using two model multimetallic systems, namely iron(III)-titanium(IV) and titanium(IV)-zirconium(IV). Use of a multimetallic composition led to increased film deposition and a variation in film morphology, compared to the monometallic systems. Importantly, the film metallic composition closely reflected that determined during assembly, demonstrating facile tuning of metallic composition and thus design of MMPN materials. In combination, it is envisaged that these fundamental insights will facilitate future application of CAP-ATRP and MMPN assembly methods for future versatile thin film engineering.
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ItemAssembly of therapeutic carriers for sustained delivery of neurotrophins to the cochlea( 2013)Gradual degeneration of auditory neurons following sensorineural hearing loss is normally caused by a depleted supply of neurotrophins, as a result of the death of the cochlear hair cells, which secrete the signaling proteins. Animal studies show that the neurodegeneration could be prevented by exogenous administration of neurotrophins, which include brain derived neurotrophic factor (BDNF), glial cell-line derived neurotrophic factor (GDNF), nerve growth factor (NGF) and neurotrophin -3 (NT-3). Optimum therapeutic benefit, however, requires continuous administration for a prolonged period. Although many novel delivery strategies (e.g. gene therapy, mini osmotic pumps and polymer hydrogels) have been previously proposed, none has been utilized at the clinical stage due to concerns about safety, cost and insufficient protein release. The primary focus of this thesis is the assembly and characterization of therapeutic carriers for the sustained delivery of neurotrophins to the cochlea. The study investigated two different carriers, namely capsosomes and calcium carbonate (CaCO3) supraparticles, by characterizing their loading capacities, as well as their long-term release kinetics in simulated physiological conditions, using lysozyme as a model protein and the BDNF. The capsosomes were prepared by incorporating liposomal compartments within hydrogel capsules using the layer by layer (LBL) assembly method, while the CaCO3 supraparticles were prepared by the evaporation initiated self-assembly of mesoporous calcium carbonates particles. The release of the proteins from the capsosomes was mainly dependent upon the composition of the liposomal compartments, while particles size and porosity governed the release from the supraparticles.
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ItemExamining the viability of geopolymer concrete: carbon dioxide emissions and key attributes( 2012)Concrete underpins ancient and modern engineered cities, and combined with steel is a key material used in modern construction. Architects have the capacity to influence the uptake of energy efficient systems used in construction. The 3.3 billion tonne p.a. Portland cement industry generates almost 10% of global anthropogenic carbon dioxide emissions. With the latent and rapid industrialisation of China and India and other developing countries, cement demand is projected to double to 6 billion tonnes p.a. by 2050. An alternative technology, geopolymer, uses an alkali activator which combines high portions of industrial by-product to form an alternative binder for concrete. There is much debate in industry regarding the environmental and structural performance of geopolymers. This thesis re-evaluates the carbon dioxide emissions associated with geopolymers, and examines key material attributes affecting viability. The appropriate manufacturing path for the alkali activator can achieve a reduction in carbon dioxide emissions of 59 - 92% compared to Portland cement. At present there is some limited commercial uptake of geopolymer concrete in select markets such as Russia, Australia and China. However, there is no wide global-scale utilisation. Barriers and opportunities for uptake are reviewed in this thesis. A saving of 600 billion tonnes of carbon dioxide emissions over the next four decades will be needed to achieve the stabilisation of greenhouse gas emissions concentrations between 450 and 550 parts per million of carbon dioxide emissions equivalent. With this mounting challenge, combined with the activation of global carbon markets predicted to be worth in excess of AUD 1 trillion within 5-10 years, there is likely to be growing interest in cement sector technologies which can deliver major reductions in carbon dioxide emissions.
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ItemA novel approach towards dynamic cross-linked hydrogels( 2012)Expanding interest in supramolecular polymer chemistry has allowed access to a wide range of materials with sophisticated molecular architectures. ‘Sliding-ring’ (SR) hydrogels are based on the non-covalent interaction between α-cyclodextrin (CD) and poly(ethylene glycol) (PEG). Intermolecular cross-linking between the CDs results in networks, where the cross-link points are dynamic in nature. Due to the rotational and translational freedom seen in these cross-link points enhanced mechanical properties are observed. However, since their inception the synthetic approach towards these SR networks has not diverged significantly with numerous isolation and purification steps still being required. This thesis presents a facile one-pot route towards the synthesis of SR networks. The innovative approach results in SR networks where a single CD moiety acts not only as the moveable cross-linker, but also as the end-capping agent which prevents the dissociation of the inclusion complex. Network formation is induced via the copper-catalysed azide-alkyne cycloaddition (CuAAC) form of click chemistry between azido functionalised α-CDs and alkyne functionalised PEG. The resultant networks are characterised in terms of their physicochemical properties such as swellability and mechanical strength. Due to the one-pot nature of the synthetic approach and the fact that inclusion complexation is in dynamic equilibrium, the resulting networks possess both SR and covalent cross-link points. Model studies were conducted whereby a series of rotaxanes were synthesised using the same reagents and under similar curing conditions as for the SR networks. From model studies, an estimation of the extent of SR links within the network was obtained.
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ItemA new paradigm in near-net-shape advanced ceramic components processing: development of the novel processing technique( 2011)There are two general ways of processing ceramic materials namely dry and colloidal (wet) processing technique. The colloidal processing route has been widely studied and known to produce better ceramic articles. However, the process of removing the solvents through drying by heating them at high temperature is highly energy intensive (especially if the solvent is water). This thesis will discuss an alternative route using high vapour pressure organic solvents to speed up the solvent removal process. This route involves the reduction in pressure (by applying vacuum) to promote drying as oppose to heating. The surface of alumina which is inherently hydrophilic was made hydrophobic through alkylation reaction with alcohols (chem-adsorbed suspensions) or addition of polymers (phys-adsorbed suspensions) such as Hypermer A70 or Solsperse 3000. The purpose of manipulating the surface chemistry was to enable the dispersion of alumina in the organic solvents such as dodecane, cyclohexane or pentane. The viscosity of suspensions was found to decrease with the increase in the length of the stabilising molecules. This was consistent with the calculated reduction in the inter-particles attraction as the extent of the stabilising molecules increases. A high solid loading of alumina (50%vol) in dodecane using Hypermer A70 (3%wt) was achieved while maintaining a low viscosity (0.25 Pa.s at 100s-1). The observed rheological behaviour fitted the Quemada viscosity model quite well when the effective volume of the polymer was accounted for, which indicated the absence of depletion attraction due to the unadsorbed polymer. The optimum concentration of Hypermer A70 was determined using UV-Visible Spectroscopy technique and was found to be 2.8%wt. The vacuum moulding process produced an interesting and intricate formation of macroscopic voids or channels instead of cracks inside the green body upon the removal of pentane. The fraction of the void space was found to decrease linearly with the increase in the initial solids concentration. By extrapolating this relationship, it was shown that the void space should disappear when the initial solid concentration of the suspension was 62.3% vol. Density measurements performed on the denser sections of the green body showed that the density values were very close to the maximum close packing of spheres (on average 60.7% of the theoretical density). This result is also consistent with the data from the air-driven filtration where the volume fraction of the cake (in essence, the green body) was found to be 64.1%, when the suspension was consolidated by the maximum capillary pressure. The close proximity of these values suggests that they are self-consistent and the dense part is consolidated by the capillary pressure at the same time as the formation of channels. The formation of these voids or channels was thought to be a drying-rate dependent process. It was possible to achieve the green and sintered densities of up to 65.7% and 97.1% theoretical density, respectively, when the rate of removal was slowed down.
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ItemShrinkage behaviour of geopolymer( 2009)Geopolymer cements offer an alternative to, and potential replacement for, ordinary Portland cement (OPC). Geopolymer technology also has the potential to reduce global greenhouse emissions caused by OPC production. There is already a considerable amount of work and research conducted on geopolymers in the past decades, and it is now possible to implement this technology commercially. However, to ensure that geopolymer becomes commercially available and able to be used in the world, further understanding of its ability to provide durable and long lasting materials is required. One main property which is still relatively unexplored compared to other properties is its shrinkage properties. The objective of this thesis is therefore to examine the shrinkage of geopolymers and factors which might influence it. The factors which influence geopolymer strength were investigated as being the factors which may influence shrinkage. The selection of the activating solution is an important factor in forming the final product of a geopolymer. Activating solution SiO2/Na2O ratio is determined to be an important influence on the shrinkage of geopolymer. SEM images of the samples enable observation of the sample topology and microstructure. An important observation was the existence of a ‘knee point’ which also occurs in OPC shrinkage. The ‘knee point’ is the point where the shrinkage goes from rapid shrinkage to slow shrinkage. From SEMs it is noted that the samples past the knee point are shown to have a smoother topology which means it is more reacted. Autogenous shrinkage is an important issue for OPC containing a high amount of silica, and is also a key factor in geopolymer shrinkage. Autogenous shrinkage is tested by keeping samples in a sealed environment where water lost to drying is kept to a minimum. It is noted that sealing and bagging the samples reduces the shrinkage considerably. The water to cement ratio, which is an important factor in OPC shrinkage, is also explored for the case of geopolymers. Water content plays an important role in determining early stage shrinkage, and has little to no effect on the later stage shrinkage. The water loss from the samples during drying on exposure to environment is noted and compared. The addition of more water did not necessary means that more water was lost. Addition of slag is known to be beneficial to geopolymers by giving early structural strength and faster setting time. Commercial geopolymer concrete will also include the use of slag. However, the addition of slag up to a certain extent gives a deleterious affect on shrinkage. A different type of Class F fly ash source with different composition data was used to see its effect on shrinkage, with only a slight influence observed between the two ashes tested. Fly ash was also ground for different lengths of time before use in geopolymerization, with grinding for less than 12 hours giving higher shrinkage than an unground sample, but shrinkage the decreasing with grinding for 18 or 24 hours. This initial higher shrinkage has been attributed to the mechanism of grinding which resulted in unevenly shaped fly ash particles taking up a larger initial volume resulting in higher shrinkage. The sample grinded for 24 hours showed higher shrinkage due to the particle size to be so fine that agglomerates may have form during mixing which would result in a lower reaction rate which increases the shrinkage. Elevated curing temperatures also reduce geopolymer shrinkage. Thus, it is clear that the shrinkage of geopolymers is influenced by a wide range of variables, and more notably by a few important variables: activating solution ratio, addition of water, grinding and bagging. The shrinkage of geopolymers can be correlated to the strength to a certain extent. However, the understanding of the shrinkage of geopolymers is still at a very initial phase, and further research is required.