Chemical and Biomolecular Engineering - Theses
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Engineering Particle Systems for Pulmonary Delivery
Pulmonary delivery has proven to be a promising delivery route for either local lung targeting or systemic delivery. A variety of particle systems such as polymeric particles and lipid-based particle systems have been developed as therapeutic delivery carriers for pulmonary delivery. However, the majority of current inhaled particles have limited retention time and low bioavailability in the target lung region, leading to suboptimal efficacy of therapeutic delivery and needing increased drug dosage or dose frequency, which could cause severe side effects. This is mainly due to the clearance and metabolic degradation mechanisms in the lungs. The mucociliary clearance and the alveolar macrophage clearance defend the airway and deep lung region, respectively, and are responsible for the elimination of inhaled particles. Therefore, it is important to understand the interactions of particles with the complex lung physiological environment in order to design more effective drug delivery carriers that can overcome various biological barriers or exploit the defence mechanisms to achieve improved biological outcomes. This PhD thesis focuses on engineering particle systems for pulmonary drug delivery, with specific aims of studying the interactions between inhalable particles and complex biological systems in the lungs including particle–mucus interactions and the role of a pulmonary corona in the uptake or clearance of particles by alveolar macrophages. Poly (ethylene glycol) (PEG) as a low-fouling material commonly used for ‘stealth’ modification of particles to reduce immune clearance was first investigated. The use of PEG building blocks with various architectures resulted in PEG-based particles with different structures and mechanical properties, which further affected the interactions of particles with proteins and immune cells in a complex biological environment (e.g., human blood). The particle–mucus interactions were then studied in the second part of this PhD research by comparing different polymer particles with potentially mucoadhesive and mucus-penetrating properties, obtaining a basic understanding of mucociliary clearance of particles in the lungs. The role of the pulmonary protein corona in alveolar macrophage clearance of polymer particles was then studied. The presence of a protein corona on particles resulted in increased or reduced macrophage uptake depending on the particle properties. When particles were transferred from one biological environment into another (e.g., blood to lungs), the interplay of protein coronas formed in each environment determined the composition of the eventual mixed protein corona and the subsequent particle–cell interactions. Finally, drug (structurally nanoengineered antimicrobial peptide polymers) loading and intracellular delivery using promising polyphenol-based carriers were investigated as potential antimicrobial therapies against lung infections (e.g., tuberculosis).
Whey Management for the Dairy Industry: Acid and Salty Whey Treatment and Processing Using Membrane Technology
Acid whey and salty whey have presented a major disposal issue for the dairy industry. The processing of acid whey has proven challenging due to the presence of lactic acid and high levels of minerals, while salty whey is underutilized due to the high levels of salt. The treatment of these two types of whey will allow the production of high value products, including whey powders, lactose powder, and concentrated salt solutions for use in cheese salting or the chlor-alkali industry. The use of membrane technology has been studied for the treatment and processing of these whey streams. Electrodialysis has been shown to be effective for the treatment of acid whey since the process can achieve high removal of lactic acid and minerals when compared to pressure driven membrane processes, such as nanofiltration. However, electrodialysis is not used widely due to the high operating costs associated with membrane replacement and electrical consumption as a result of membrane fouling and poor process performance. In this thesis, the fouling of ion-exchange membranes during the electrodialysis of fresh sweet and acid whey was investigated. Although the fouling of ion-exchange membrane has been examined by many researchers, the feed solution was generally made using resolubilised powders. It has been demonstrated by other researchers that using fresh solutions provide results and outcomes closer to industrial applications. Furthermore, process optimization is a key parameter to reduce the cost of the treatment process. As a result, the effects of concentrate pH and applied current density were investigated to determine the optimum operating conditions that would minimize membrane fouling and enhance ion removal. Although membrane fouling occurred in all experiments, the effects on system performance were limited. Reductions in the current during pure sodium chloride circulation fell to a minimum of 80% of the original value after 5 hrs of whey processing. The use of an alkaline concentrate resulted in the strongest increase in system resistance, but the mineral deposits formed appeared to detach readily, thereby reducing these effects. The use of an acidic concentrate gave significantly greater rates of lactic acid removal, thus reducing the total membrane area required. A solution of hydrochloric acid with a pH of 1.0 was effective for in-situ cleaning of the mineral deposits. However, protein deposits were not readily removed when using the recommended base cleaning formula of 3% sodium chloride at a pH of 9.2. The concentrate stream in an electrodialysis process is considered a waste stream thus adding to the total volumes of waste generated by the dairy factory. Therefore, the use of salty whey permeate as the concentrate stream was investigated during the electrodialysis of sweet whey. The use of salty whey permeate is expected to reduce freshwater update and the volumes of wastewater generated from the treatment process. The type of concentrate (0.1M sodium chloride or salty whey permeate) did not affect the rate of sweet whey demineralization or the energy consumed per tonne of sweet whey processed, but less sodium and more divalent cations were removed when salty whey permeate was used. In addition, the use of electrodialysis for the demineralization of salty whey permeate was investigated to generate a lactose rich stream as the diluate stream and a concentrated salt solution as the concentrate stream. It was observed that salty whey permeate could be effectively demineralized using either 0.1M sodium chloride or a second stream of salty whey permeate as the concentrate stream. The concentrate purity could be enhanced by using monovalent selective membranes without increasing the energy consumption of the process (3.2 kWh per kg of sodium chloride removed from the diluate at 15 V across 2 cell pairs). Furthermore, combining different membrane technologies can assist in enhancing the treatment of acid whey to produce high quality whey powder. Three process combinations were examined at pilot scale, namely, (1) ultrafiltration and electrodialysis; (2) ultrafiltration, nanofiltration, and electrodialysis; and (3) ultrafiltration, dia-nanofiltration, and electrodialysis. Although all three combinations were successful in reducing the levels of lactic acid and minerals in acid whey, the lowest ratio between lactic acid and lactose (0.017 g lactic acid/g of lactose) was obtained with the process that utilized dia-nanofiltration. The energy required for the electrodialysis of the ultrafiltration permeate and dia-nanofiltration retentate were comparable (7.5 and 7.8 kWh/tonne of feed, respectively). However, the dia-nanofiltration retentate was at least 3.5 times more concentrated than the ultrafiltration permeate, thus reducing the annual energy consumption and capital investment of the electrodialysis unit. The product of the nanofiltration and electrodialysis process was successfully dried to produce a powder with an ash and moisture content of 4% and 2.5%, respectively. To further add value to the acid whey treatment process, the possibility of recovering lactic acid from a salt solution was investigated using either loose reverse osmosis membranes or an electrodialysis process. The recovered lactic acid could be reused in the cheese making process thus reducing fresh acid intake. Partial separation between lactic acid and salts was achieved at low applied pressures and feed pH in the reverse osmosis process, as a greater permeation of salts was observed under these conditions. Furthermore, lactic acid retention was enhanced by operating at room temperature with low feed pH. Partial separation between lactic acid and potassium chloride was also achieved in the electrodialysis process. However, the final concentration of potassium at 70% demineralization of the diluate stream was relatively high resulting in a low purity of lactic acid. Furthermore, the observed losses in lactic acid increased with the addition of sodium chloride to the feed solution. This indicates that the separation becomes more challenging as the complexity of the feed solution increases. Although electrodialysis has been widely studied for the treatment of sweet and acid whey, other electrically driven membrane processes, such as membrane capacitive deionization, have never been investigated. Three different pre-treated acid whey solutions were processed through a lab scale membrane capacitive deionization unit, namely, ultrafiltration permeate, nanofiltration retentate, and dia-nanofiltration retentate. Although a lowest demineralization rate was calculated for the nanofiltration retentate, a higher removal of lactic acid and cations was achieved when compared to the ultrafiltration permeate. Furthermore, similar molar concentration of ions were removed from the ultrafiltration permeate and dia-nanofiltration retentate (41 mEq/L and 43 mEq/L, respectively), however, the total energy consumption was lower for the dia-nanofiltration retentate (0.0122 Wh/mEq of cations removed Vs 0.0243 Wh/mEq of cations removed from the ultrafiltration permeate). Finally, it was found that the energy consumed for the treatment of acid whey ultrafiltered permeate using membrane capacitive deionization was comparable to the energy reported for the electrodialysis process. Overall, the results presented in this thesis have demonstrated that both acid whey and salty whey can be treated and transferred into valuable products for the dairy industry. Future work on this topic could include: (1) investigating the feasibility of using electrodialysis reversal for acid whey treatment; (2) performing a pilot scale assessment of the membrane capacitive deionization process; (3) undertaking an economic evaluation to justify using pressure driven membrane process prior to electrodialysis and membrane capacitive deionization processes; and (4) reassessing the possibility of recovering lactic acid from a salt solution by using other available technologies/ processes such as electrodeionization and selective crystallization of lactic acid.
Engineering catalytic organic-inorganic materials for sensing applications
Nanostructured hybrid organic-inorganic materials are a unique class of materials showing distinctive properties that have attracted high interest due to their diverse applications in the fields of energy, environment and medicine. In particular, hybrid materials are promising candidates for sensing applications due to the tunable chemical, structural and functional properties of the organic and inorganic components. Hence, the engineering of novel nanostructured catalytic organic/inorganic materials provides opportunities for the fabrication of advanced nanodevices for biosensing. In this thesis, novel hybrid materials have been prepared and their electrocatalytic, catalytic, and optical properties explored. First, nanostructured electrocatalytic microparticles were synthesized in mild conditions and used with an organic binding agent to prepare carbon electrodes applied in the detection of glucose in biologically relevant media. Second, hierarchically structured hybrid particles displaying enzyme-like catalytic activities were synthesized and used to prepare high-throughput micro-reactors for the detection of bioanalytes via a hybrid organic-inorganic cascade reaction. Finally, a natural occurring polysaccharidic nanoparticle, i.e. glycogen, was engineered to impart adhesive functional properties to a hybrid film and used for the coating of various substrates with different chemical composition. These hybrid coatings embedding metal nanoparticles were employed as catalytic and optically active functional interfaces.
Nanoengineered Drug Delivery Systems for the Treatment of Sensorineural Hearing Loss
Inner ear disease is the leading cause of hearing impairment in developed countries. An estimated 466 million people suffer from hearing loss worldwide and this number is on the rise. Sensorineural hearing loss (SNHL) is the most common form of hearing impairment and is characterised by the degeneration of key structures of the sensory pathway in the cochlea of the inner ear (the cochlea) such as the sensory hair cells, the primary auditory neurons and their synaptic connection to the hair cells. Current research focuses on developing techniques to administer growth proteins such as neurotrophins to repair or regenerate damaged auditory neurons, as well as preventing loss of primary auditory neurons. Drug delivery systems are being developed to treat SNHL, such as cell-based drug delivery systems and gene vectors, however nanoengineered systems show promise to address the specific needs of neurotrophin-based therapies such as safety, high dosing and long-term delivery to the cochlea. Research carried out in this thesis has developed this technology further by the scale-up production of nanoengineered silica-based supraparticles (SPs) (~550 micrometers) with high porosity) and the development of several strategies towards their application as viable drug delivery platforms for achieving sustained drug release in the inner ear, as detailed in Chapters 3-6. In Chapter 3, a gel-mediated electrospray technique was developed to synthesise silica supraparticles (Si-SPs) in high yields. The Si-SPs were assembled from different primary silica particles i.e., particles with no pores, small pores (2-3 nm) and bimodal large pores (2-3 nm and 15-64 nm). A high loading of fluorescently labelled model protein (fluorescein isothiocyanate (FITC)-lysozyme) and neurotrophic factor (a drug for the treatment of inner ear disease) in the Si-SPs was possible and the resulting particle system could achieve sustained drug release for over 150 days. The findings demonstrate that gel-mediated electrospray is a robust and automatable technology to produce Si-SPs, which is a promising platform for clinical translation and commercialisation. In Chapter 4, the pharmacokinetics of the neurotrophin brain-derived neurotrophic factor (BDNF) from Si-SPs was examined as engineering drug delivery systems with well-defined pharmacokinetics is important for clinical translation. BDNF-loaded Si-SPs were surgically implanted either directly into the cochlea, or onto a semi-permeable membrane (the round window membrane; RWM) that is a boundary between the middle and inner ear. Treatment duration was for either 3 or 7 days whereby the fluids from the cochleae were sampled and tested for BDNF levels. The results showed that the BDNF released from the Si-SPs was detected in the cochlear fluids indicating that the approach has potential as a clinically relevant neurotrophin delivery strategy to treat people with hearing impairment. In Chapter 5, a bioengineering coating strategy was developed for retarding the initial burst release of neurotrophins from the Si-SPs. Applying a fibrin coating on the surface of the Si-SPs and embedding the fibrin-coated Si-SPs within an alginate CaCO3 hydrogel both slowed the initial burst release to improve the drug release kinetics. The results demonstrate the suitability of alginate CaCO3 hydrogel systems for surgical handing of the Si-SP system. In Chapter 6, a chitosan and an alginate layer-by-layer coating on the Si-SPs was developed as an alternative strategy for delaying the initial burst release of uncoated Si-SPs. Chitosan and alginate are two biocompatible polysaccharides that interact electrostatically via the carboxyl groups from alginate (negatively charged) and the amine groups on chitosan (positively charged). By varying the layer number and hence, the thickness of the coating, different release profiles were attained. In vitro neurotrophins release profiles showed that chitosan-alginate-coated silica supraparticles ((Chi/Alg)Si-SPs) experienced a delayed initial burst release. Spiral ganglion neurons culture and neurite length analysis indicated that the neurotrophins released from (Chi/Alg)Si-SPs had maintained biological activity. Functional hearing was tested using auditory brainstem responses (ABRs) to determine the safety profile of surgical delivery of coated SPs to the inner ear. Hearing thresholds were maintained within the normal range following RWM, however an increase in thresholds for high frequency sounds were observed following implantation of (Chi/Alg)Si-SPs into the cochlea. Scanning electron microscopy images of (Chi/Alg)Si-SPs collected following in vivo implantation along with a commercial viable fibrin sealant indicated the biodegradability of (Chi/Alg)Si-SPs post-implantation. These results indicate that (Chi/Alg)Si-SPs can potentially be used as a clinically applicable platform for sustained inner ear neurotrophin delivery. In summary, this thesis expands knowledge in the development and engineering of Si-SPs in addressing key neurotrophin delivery issues for the treatment of hearing loss, including high yield, sustained drug release, well-defined pharmacokinetics and biodegradability.
Cytochrome P450-mediated biotransformation of noscapine
Cytochrome P450 enzymes are promising biocatalysts for the pharmaceutical industry due to their ability to catalyse selective oxidations of drug-like substrates that are often difficult to achieve with synthetic organic chemistry. This enzyme family is, however, currently underrepresented in industrial biocatalysis due to issues with enzyme stability and cofactor requirements, as well as the poor aqueous solubility of many cytochrome P450 substrates. In this thesis, cytochrome P450-mediated biotransformation of the opium poppy alkaloid noscapine was used as a model reaction for the development and optimisation of a biotransformation process using bacterial cells. The aims of this thesis were to develop a biocatalytic method for the production of noscapine metabolites, which are of interest for the development of anticancer drugs, and to investigate strategies for the implementation of cytochrome P450s in pharmaceutical manufacturing processes. In order to obtain a suitable P450 enzyme for the biotransformation of noscapine, a library of mutants of the enzyme P450BM3 from Bacillus megaterium was constructed using site-directed mutagenesis. This strategy identified enzyme mutants capable of producing six different noscapine metabolites, several of which may be of interest for drug development. A high selectivity for noscapine N-demethylation was demonstrated by several mutants. This N-demethylation reaction was therefore selected as a focus for further process development in a whole-cell biotransformation system. The permeability of Gram-negative and Gram-positive bacteria to noscapine was assessed in order to minimise mass transfer limitations in a whole-cell biotransformation system. This identified Bacillus megaterium as a suitable expression host, as these cells enabled significantly faster reaction rates compared to the Gram-negative Escherichia coli. As noscapine has poor aqueous solubility, two strategies were investigated to improve substrate loading for the biotransformation. First, a biphasic biotransformation system, which uses a water-immiscible organic solvent phase to supply substrate, was developed with the use of in silico solvent screening based on Hansen solubility parameters. This was effective in increasing product yields but had the disadvantage of slower reaction rates due to substrate partitioning. The second approach used a cyclodextrin/polymer system to enhance aqueous noscapine solubility and proved more effective, enabling faster reaction rates. However, the stability of the mutant P450BM3 enzyme was found to be a major factor limiting product yield. The use of growing cells rather than resting cells was then investigated to address the limited enzyme stability observed during biotransformation. As intracellular cofactor supply can often limit reaction rates in growing cells, a metabolic engineering strategy based on the CRISPR/dCas9 interference (CRISPRi) system was used to redirect carbon flux towards cofactor production in the B. megaterium host. This provided a significant improvement in productivity compared to cells lacking the CRISPRi system, though dynamic control of gene repression was not possible due to ‘leaky’ expression of dCas9 from an inducible promoter. The CRISPRi-enhanced system with growing cells showed comparable productivity to the resting-cell system, with the advantage of sustained P450BM3 regeneration and fewer processing steps. In summary, an enzyme and host cell system for the biocatalytic N-demethylation of noscapine was developed. A number of process limitations were identified and addressed to optimise the yield and productivity of the system. The limitations that were encountered during process development are common to whole-cell biotransformations using P450 enzymes, and the strategies used to address these limitations are likely to be useful for the development of other P450-catalysed biotransformation processes.
Interfacial rheology of fluid-fluid interfaces at the micro to nanoscale with AFM
This thesis introduces and benchmarks 2 novel AFM based techniques to characterise the interfacial rheology of polymeric fluid-fluid interfaces. We develop and benchmark a time-dependent extension of capsule compression to model oscillatory indentations, determining the interfacial rheology of capsules from thin shells to thick shells. This is first tested and benchmarked using the food-based emulsifier beta-lactoglobulin at the MCT-Oil interface. This system is then crosslinked and the behavioural changes in the capsule oscillatory rheology, bicone shear rheology and pendant drop dilational rheology are tested. This investigation has shown that there is a significant frequency dependent response of beta-lactoglobulin capsules to an oscillatory indentation in both the native and the crosslinked state. We also show that there is a large indentation depth dependence on the time dependent dwell behaviour. When comparing these behaviours to the bicone shear rheology and pendant drop dilational rheology, the magnitude of the moduli at similar frequencies differs strongly between all techniques. Comparatively, the tan(delta) between the bicone and capsule measurements exhibits similar magnitudes for both the native and crosslinked cases. An extension of the capsule technique was made to include thicker interfaces, where the thickness of the interface is more than 5% of the overall capsule radius. This model was tested with the food hydrocolloid chitosan, which in acetate buffer concentrations above 0.3M makes particulates and becomes surface active, forming a thick film at the interface. We determine the properties of this film by assessing the film mechanically and visually. To mechanically characterise the film, we utilize bicone interfacial shear rheology, and both linear and oscillatory capsule compression. The film exhibits characteristic particle like behaviours and rapidly heals when broken in shear. Similar self-healing characteristics are then observed in the linear capsule compression, and the oscillatory capsule compression shows similar moduli and behaviour to that observed by the bicone. The visual characterisation was done with in-situ aqueous imaging and dry Langmuir-Blodgett imaging of a transferred film, where a thick, continuous, particulate film is observed. We continue to push the lengthscale of interfacial rheology by developing a novel method of observing the interfacial rheology at a fluid/fluid interface. This method consists of placing a cantilever tip at the interface between two fluids, laterally translating the tip and observing the torsional force on the cantilever. This force can then be transformed into an interfacial viscosity with the knowledge of the diameter of the tip at the interface. We apply this technique to two types of interfaces, linear polymeric interfaces and a globular protein interface. At the air/water interface, we test the linear polymers PEO and PSS, where we observe that shorter chain length PSS shows a reduction in the interfacial viscosity. beta-lactoglobulin is observed over time at the decane/water interface, where the interfacial viscosity increases over time, and non-linear strain dependent behaviour is observed.
Material-based gene therapy approaches for HIV and neurodegenerative diseases
Gene therapy is of interest in medicine as it allows potential treatment of inherited and acquired diseases that cannot be treated or prevented using conventional methods. The introduction of new genetic material into the cells aims to improve cellular functions by either replacing a malfunctioning gene with a functional transgene or silencing the expression of specific genes implicated in various human diseases. The delivery of plasmid DNA provides an opportunity to replace defective or missing genes by utilizing cellular gene expression apparatus to produce encoded proteins. RNA therapeutics act via the RNA interference pathway to target intermediate gene expression product for degradation and prevent its translation to protein. Free nucleic acids typically experience rapid blood clearance and a short circulation lifetime and are unable to cross biological membranes due to electrostatic repulsion between DNA/RNA phosphate groups and phospholipids in the cell membrane. Therefore, there is a need to formulate gene carriers for improved pharmacokinetics of DNA/RNA therapeutics and efficient delivery to the site of action. The main objective of this research project was to develop material-based systems for gene delivery and apply it to HIV therapy and Friedreich’s ataxia (FRDA). Polyarginine-containing capsules were prepared via layer-by-layer assembly and enabled efficient complexation of anti-HIV siRNA. The functional effect via transcriptional gene silencing of the viral genome was demonstrated in virus-infected primary cells. To investigate how cellular changes associated with cell activation and viral infection influence the particle-cell interactions, particles association with activated primary cells and pseudovirus-infected T cells was investigated. In the second part of the thesis, the optimization of DNA binding by polyarginine-containing LbL core-shell particles and the delivery of frataxin-encoding plasmid DNA to address the FRDA-associated frataxin depletion was demonstrated using patient-derived iPSC neurons. The role of particle size, charge and density in the interaction of particles with iPSC 3D neuronal organoids was also demonstrated. This thesis presents the preparation and characterization of LbL-assembled particles as a versatile system with easily tailorable properties and its application in gene therapy for viral and neurodegenerative diseases. The presented research also aims to gain a fundamental understanding of bio-nano interactions in various biological systems.
Controlled cracking in multilayered graphene films coated on flexible substrates and their electromechanical properties
Cracking in the brittle thin films causes tremendous trouble, but controlling cracking with care brings new opportunities to flexible electronics, particularly the highly accurate strain sensing. However, the complexity of the influencing factors on crack formation poses challenges to research, accurate control, and the full utilization of the novel cracked-thin film strain sensor. Multilayered reduced graphene oxide (MLG) films, due to their tuneable structural parameters via wet fabrication and high electric conductivity, could potentially serve as a promising material platform to study the cracking behaviours and the corresponding electromechanical properties. In particular, their unique cascading 2D nanostructures may lead to unusual cracking behaviours and advantageous electromechanical properties. Thus, this dissertation aims to explore the cracking behaviours of ultrathin MLG films coated on a stretchable substrate and the electromechanical properties of the cracked thin films. This project unfolds into three parts. In the first part, the method to coat the vacuum filtrated ultrathin MLG film on a flexible substrate is developed. By utilizing a swelling-induced interfacial effect of graphene oxide, we developed a simple method to manipulate the surface adhesion between the MLG film and the filtration membrane, allowing the MLG film with high surface quality to be readily coated on a series of substrates through a simple transfer printing process. The second part investigates the cracking behaviours of the MLG film transferred on a polydimethylsiloxane (PDMS) substrate. The cracking morphology of MLG films was found to depend on thickness, interlayer distance, and corrugation. An unexpected transformation of cracking morphology from typical “parallel” cracks to random “percolative” cracks was observed when the MLG film is very thin (< 40 layers of reduced graphene oxide). The third part further explores the electromechanical properties of the cracked MLG films. A high gauge factor (GF) of 56521 at strain = 6 % and large stretchability of strain = 60 % when GF = 5.1 were achieved for the parallel cracked and highly percolative cracked MLG films, respectively. The static and dynamic electromechanical characterization indicates that the percolative cracking could readily reduce relaxation, allowing accurate strain detection. A broad-frequency range accurate strain detection is demonstrated, suggesting their potential applications in human-machine interfacing and neuromuscular disease detection.
Mechanochromic Polymeric Materials Based on Spiropyran
Smart chromic materials which change colour due to an external stimulus such as light, mechanical force, temperature and humidity have great potential in commercial applications including as sensors, coatings and drug delivery. Mechanochromic polymeric materials, those polymeric materials which respond to an applied force, are one of the most widely studied and one strategy for their preparation is to covalently bond a mechanochromophore such as spiropyran (SP) into a polymer matrix. Spiropyran when constrained in this way, undergoes a ring-opening reaction to form brightly coloured merocyanine (MC) isomer when subjected to an external force. Although SP has been integrated into a wide range of polymers, lacking the detailed understanding of the factors that affect their mechanochromic properties and challenges in achieving high mechanochromic sensitivity of these systems have limited their practical applications. The goals of this thesis were to explore the factors affecting the mechanochromic efficiency of SP to MC and design advanced polymer architectures to improve their mechano-sensitivity. In Chapter 2, a new tri-functional SP (SP3) combining the attachment positions of the two most commonly used SPs (SP1 and SP2) was synthesized. The three SPs (SP1-3) were subsequently crosslinked into the same non-polar polydimethylsiloxane (PDMS) polymer and their mechanochromic properties induced by compression and tension were evaluated. The influence of varying the functional group attachment to the matrix resulting in the geometric and electronic changes on their mechanochromic properties were investigated. The outcome of this investigation determined that of the two factors influencing the mechanochromic responsiveness of the materials, the geometric effect was more dominant than the electronic effect. Typically the majority of mechanochromic SPs are conjugated in non-polar matrices for their studies, however in Chapter 3, we studied the incorporation of SPs (SP1-3) into polar poly(hydroxyethyl acrylate) (PHEA) polymer and studied their unique mechanochromic properties and negative photochromism due to the polar environment. In this investigation the mechanochromic materials were triggered by the force induced by swelling in water. The results demonstrated that SP3 with more attachment points was the least affected by the polar environment and it showed the fastest mechanoactivation during swelling. Following on from the swelling-induced mechanochromic advantages observed for SP3, in Chapter 4, a multi-network structure of polyacrylates was adopted to incorporate this mechanophore into a pre-stretched first-network. The resultant double network presented a remarkable mechanochromic activity, where the corresponding SP-linked single network showed no colour change. The activation energy was further reduced by the formation of a third-network. This SP-linked triple-network was shown to display the lowest activation energy compared to previously reported SP-linked elastomers, demonstrating a significant improvement in the mechanochromic sensitivity of these materials due to advanced architectural design. This thesis therefore provides insights into the factors influencing the ring-opening efficiency of SP to MC through the design of a new SP, and led to a new strategy towards the fabrication of highly sensitive mechanochromic SP-linked polymer. The outcomes of this research will be useful for the design of mechanochromic materials for targeted applications such as force sensors and authentication devices.
Understanding Colloidal Adhesion in Polymer Surfactant Emulsions
Attractive interactions between drops in which aggregation or adhesion occurs, rather than coalescence, govern the formation of microstructures that control the phase behaviour, stability, rheology and most importantly function of formulated products (e.g., food, personal care products, pharmaceutical formulations). These products are often multi-component emulsions where interactions between additives can mediate adhesion in complicated ways. The overarching objective of this thesis was to understand how polymer-surfactant (PS) complexes mediate adhesive interactions, with a focus given to the development of a novel microfluidic platform capable of investigating these systems using high throughput measurements. The attractive interactions between oil drops in poly(vinylpyrrolidone) (PVP) and sodium dodecyl sulphate (SDS) solutions were studied using both drop chaining in a microfluidic device and direct force measurements on an AFM. Links between the two methods were explored in detail with emphasis on understanding and establishing similarities in surface coverage and the structural composition of layers at the drops interface. Through interfacial tension measurements, direct force measurements and microfluidic observations a detailed investigation into drop-drop interactions was performed. Interfacial tension measurements confirmed the formation of PS complexes and the concentration region in which they exist for the PVP/SDS system. Rigid force measurements showed via a quantitative model that depletion and electrical double layer (EDL) forces dominate the interactions between two hydrophobic surfaces. Force measurements between two deformable oil drops using the same systems displayed similar depletion behaviour. A model used to describe deformable systems, also accounting for depletion and EDL forces, used the depletion length and osmotic pressure fit from the rigid surface analysis and showed reasonable agreement with the force data. A small under prediction by the model suggested the existence of an additional steric force from the presence of adsorbed complexes at the interface. At velocities above 500 nm/s dynamic forces dominated the force data, such that it was no longer possible to observe the force features in the measurements. A microfluidic device designed with a drop collision region, allowing drops to come into close separation in the absence of hydrodynamic drainage forces was developed to form chains of oil drops. The persistence and length of a drop chain within a simple external flow was associated to the strength of adhesion across a range of solution compositions and concentrations, independently demonstrating the existence of attractive forces between drops in the PVP/SDS system. The interaction behaviour between the two techniques showed a strong correlation, where the observed adhesion between drops in the microfluidics is sensitive to the drop deformation and Laplace pressure. Microfluidic interfacial tension measurements were used to investigate the adsorption kinetics of the PVP/SDS system and surface chemistry of the drops in confined flow via the measurement of a drops deformation through a channel contraction. The continuous phase viscosities of the investigated systems were substantially lower than those used in previous studies, requiring much higher flowrates to be used to achieve measurable deformation. The interfacial tension values attained from microfluidic measurements agreed well with pendent drop experiments, showing characteristic features expected from polymer surfactant systems in interfacial tension measurements. A series of five contractions, where the interfacial tension was measured at increasing time intervals, showed that the interfacial tension reached a time invariant value within milliseconds. These results give reasonable evidence that the PS complex adsorbs to the interface in microfluidic flow at similar levels as the AFM measurements and within relevant timescales. Droplet microfluidic SANS using a novel device provided information on the molecular structure of the complexes in solution and at the interface. Scattering from the single-phase solutions of PVP, SDS and their complex was successfully measured and showed characteristic intensity patterns expected from each condition based on reviews of the literature. Detailed quantitative analysis of each condition was performed, providing information on their confirmation and evidence of shear-induced transformations. Droplet microfluidic SANS was qualitatively assessed, showing clear differences to bulk single-phase data of equivalent solutions, suggesting evidence of changes to the scattering characteristics which is predicted to be due to an adsorbed layer. At this time the structure or composition of this layer beyond an estimated thickness were unable to be attained as models capable of fitting these specific measurements are not available. Nevertheless, these results provided a consistent picture of an adsorbed PS layer under flow as seen with the other techniques explored throughout this thesis.
Metal-phenolic assembly for engineering multifunctional materials: Beyond hard templates
Metal-phenolic coordination assembly for the fabrication of multifunctional materials for diverse applications, including catalysis, pharmaceutical, nanomedicine and sensing, has attracted much attention in recent years. However, the bulk of the literature of metal-phenolic materials has been focused on the assembly on hard templates using a single ligand. There is a scope in advancing the field by investigating the versatility of the assembly system in terms of different phenolic ligands, templates and assembly techniques, which could result in novel multifunctional materials. In this thesis, different assembly techniques, particularly the use of hard and soft templates and self-assembly, were explored to create metal-phenolic materials, including thin films and particles. Metal-phenolic assembly on traditional hard templates but using a complex multicomponent phenolic mixture was first investigated (Chapter 3). The metal–phenolic assembly exhibits selective properties in a series of complex multicomponent systems (including crude plant extracts), in which metal ions (FeIII) selectively assembles with low abundant but multivalent phenolic compounds (e.g., myricetrin and quercetrin) to form thin films. This selective property was independent of the substrate properties (e.g., size, morphologies and surface charge) and the resultant metal-phenolic films demonstrated promising antioxidant properties. In Chapter 4, the transition from hard templates to microemulsions (soft) templates is described. Here, pH-sensitive poly(ethylene glycol) nanoparticles with tunable sizes and morphologies were synthesized by adjusting metal-phenolic crosslinking within the microemulsions. In Chapter 5, a template-free assembly technique was also explored to create metal-phenolic particles, which can sense and swim towards an external light source with the velocity tunable by light intensity. Nuclear magnetic resonance, confocal Raman microscopy and quantum mechanics calculations provided insight of the mechanism of light-induced movement of the metal-phenolic particles. Altogether, the metal-phenolic materials engineered through different assembly approaches presented herein show well-tailored structures and unique properties for various biomedical and engineering applications.
A narrow pore zeolite: ZSM-25 for natural gas purification
Due to both increased greenhouse gas emissions and increased natural gas demand, the development of separating CO2 and N2 from methane-rich streams (e.g. natural gas, biogas and landfill gas) has arisen worldwide research interest. Greenhouse gas emissions can be mitigated by post-combustion technology and switching the energy structure to CH4-based energy sources. Natural gas is the most significant source of CH4, which typically contains around 80%-95% CH4, less than 10% CO2 and N2, and small amounts of hydrocarbons. Hence, removing the CO2 and N2 is critical for purifying natural gas, with the respect of both increasing the energy density and preventing the corrosion of the pipeline caused by acid CO2 for transporting CH4. Adsorption-based capture of CO2 and N2 from natural gas has attracted tremendous interest owing to its economic advantages. Porous materials play very important roles in the adsorption process where the material is exposed to the gas mixture at high pressure and then desorbs at low pressure or vacuum. The significant index of evaluating a porous material is the selectivity, capacity, adsorption kinetics and regenerability. Narrow-pore zeolite (8MR zeolite) has significant potential in natural gas purification via pressure-swing adsorption (PSA), which is attributed to its pore size fitting between CO2 and CH4, and close to N2. Hence, the selectivity is relatively much higher than other zeolites (e.g. FAU, ZSM-5). However, the slow adsorption kinetics are limiting its application in the natural gas industry, and no zeolites have been found with preferential adsorbing N2 from CH4 at equilibrium, unable to effectively separate N2 from natural gas. This thesis describes the development of small-pore ZSM-25 based zeolites, and their applications in membrane separations. The study provides a rational strategy of designing ZSM-25 zeolite for effective CO2/CH4 and N2/CH4 separation in the natural gas purification industry. In this thesis, an extensive literature on 8MR zeolite for natural gas purification and their modification approaches has been sourced and analyzed in Chapter 1. Chapter 2 a Li+/ZSM-25 zeolite (LZZ) was developed via partial ion exchange of the Na+ with Li+. This exchange enabled higher CO2 capacity and adsorption kinetics due to higher pore volume and stronger affinity of CO2 with Li+, and the ultra-high CO2/CH4 selectivity remained. The CO2 isotherms showed deviation from typical Type I isotherm and 'breathing' behavior. This observation was explained by synchrotron in situ X-ray powder diffraction, demonstrating a gradual structural expansion induced by CO2. This expansion resulted in the increased CH4 admission in binary gas adsorption. This work enables the possibility of applying small-pore zeolites in natural gas purification which are kinetically-limited. Chapter 3 The Li+/ZSM-25 zeolite (LZZ) was incorporated into a commercial polymer Matrimid 5218 yielding a mixed-matrix-membrane (MMM). Li+/ZSM-25 was chosen as filler because of its fitting pore diameter between CO2 and CH4, which merely adsorbed CH4 while allowing considerable CO2 transport. The CO2/CH4 separation performance of the optimal MMMs at 5 wt% filler loading, showed higher CO2/ CH4 selectivity than that of the pristine Matrimid in both single- and mixed-gas separation. The dominant molecular sieving effect contributed to the increasing selectivity with increased pressure, showing unusual plasticization-resistance behavior. The optimized membrane (M-5) achieved ideal CO2/CH4 selectivity of 169, which surpassed the latest CO2/CH4 upper bound. Chapter 4 A new 'trapdoor' material K-ZSM-25 was designed for N2/CH4 separation by incorporating K+ as a 'door-keeping' cation. The extent of the temperature-dependent oscillations of the K+ cation regulated the accessibility of the cage, controlling the adsorption capacity of the material. There were distinguishable gate-opening temperatures (Ts) between N2 and CH4 molecules. Within this temperature range, N2 molecules had full access to the pathway into the cage, while CH4 molecules were hindered due to the blockage of K+. Both the experimental results and simulations demonstrated that K-ZSM-25 can achieve effective N2/CH4 separation at around ambient temperature with outstanding selectivity of over 30 in single gas adsorption and 5.7 in dynamic breakthrough simulation. The large N2 capacity, outstanding N2/CH4 selectivity, fast kinetics of K-ZSM-25, and it is readily regenerated ataround room temperature, all of which makes this adsorbent ideally suited to PSA-based industrial separations.