Engineering

Publication Search Results

Now showing 1 - 10 of 44
  • (2012) Nafea, Eman Habib Mohamed Abdel Hamid
    Thesis
    Cell immunoisolation systems are fast becoming a favourable approach to cure various challenging diseases and disorders such as type I diabetes. Although the addition of biological molecules to cell immunoisolation devices can significantly enhance their performance by supporting cell viability and function, little is known about their effects on the immunoisolating membrane properties especially its permselectivity. Therefore, this research focused on examining the effect of combining biological molecules with a synthetic polymer on the permeability of hydrogels, with a specific emphasis on encapsulation of insulin producing cells for treatment of diabetes. The research aimed at achieving an optimum balance between a controlled permselectivity and cell survival support. It was hypothesised that covalent incorporation of small amounts of model extracellular matrix (ECM) molecules, heparin and gelatin, would support cell viability without compromising the controlled permselectivity and physico-mechanical properties of the base PVA network. Varying the number of functional groups per PVA backbone successfully controlled the PVA permeability and physico-mechanical properties. A suitable degree of permselectivity was achieved by the highly crosslinked hydrogels. Covalent incorporation of heparin and gelatin at low percentage was successfully achieved without interfering with either their biofunctionalities or the base PVA properties, including its permselectivity. Moreover, the incorporated ECM analogues supported the viability and metabolic activity of pancreatic β-cell lines encapsulated for two weeks. Consequently, biosynthetic hydrogels composed of permselective PVA base material and a small amount of biological molecules show promise as immunoisolating materials for cell-based therapy.

  • (2010) Abramian, Miganoosh
    Thesis
    This study investigated retinal ganglion cell (RGC) responses to epiretinal electrical stimulation delivered by hexagonally-arranged bipolar (Hex) electrodes. In vitro experiments were performed using rabbit retinal preparations and a computational model was developed. Electrical stimulation was delivered using 50 and 125 IJm diameter platinum Hex electrodes and single-unit RGC activities were recorded differentially with extracellular tungsten microelectrodes. The majority of the responses exhibited short latencies (<5 ms) and were time-locked to the stimulus pulse. With 100 IJS/phase anodic-first biphasic pulses, threshold charge densities were 24.0 ± 11.2 and 7.7 ± 3.2 1JC/cm2 for 50 1-1m and 125 IJm diameter electrodes, respectively. The estimated chronaxie from the strength-duration relationship was 214 IJS. The short-latency responses of most cells (7/11) persisted at 200 Hz stimulus frequencies. Cell responses (7/7) were not diminished in the presence of cadmium chloride synaptic blocker. RGC responses persisted as the stimulating electrodes moved along the axonal path. Threshold profiles and response characteristics strongly suggested that RGC axons were the neural activation site. Both the model and in vitro data indicated that the lowest threshold point occurred beneath the centre active electrode and thresholds increased rapidly with lateral electrode distance across the retina, suggesting that localised tissue stimulation is achieved with Hex electrodes. Threshold profiles were dependant on the orientation of the electrodes relative to the axons. Thresholds increased up to 20 times when the electrodes were lifted 100 1Jm above the retinal surface. Low thresholds for axonal activation as well as the threshold increase with electrode displacement above the retinal surface are major concerns for epiretinal implant design. Overall, the threshold profiles predicted by the model accurately matched the experimental data obtained in this study.

  • (2011) Coxon, Rachel Ann
    Thesis
    Timely detection of signs and symptoms of congestion to allow for clinical intervention and prevent patient hospitalisation for cardiac failure has been a challenge. The breathing disorders which can manifest in congestive cardiac failure may provide an avenue for sourcing markers of congestion; however monitoring systems capable of long-term observation of patients are required. Practical, long-term monitoring systems were developed for sleep disordered breathing (SDB) in cardiac failure and for the detection of respiratory changes that may relate to impending decompensation of cardiac failure. A portable sleep monitoring device (ApneaLink, ResMed Ltd.) was evaluated against polysomnography (PSG) to characterise SDB in cardiac failure. In clinically unstable cardiac failure, the AHI of in-patients was found to vary by up to 10 events/hr over 3 sleep studies. Whilst it was challenging for patients to adopt the ApneaLink as a home monitoring tool, the severity of SDB was found to traverse multiple categories for SDB severity in out-patients. PSG was impractical to monitor cardiac failure patients on more than 1 night in-hospital. As an alternative to PSG, a test regimen for assessing Cheyne-Stokes respiration (CSR) in the wake state was developed and evaluated. Whilst the test could not differentiate patients with CSR, further modifications to the test may realise this objective. Respiratory monitoring and SDB treatment devices were investigated for the detection of respiratory changes that may relate to decompensation of cardiac failure. The parameters derived from actigraphy based sleep assessment and positive airway pressure therapy devices were found to be feasible and apparently clinically beneficial surrogate measurement methods for pulmonary fluid status in cardiac failure patients. Decompensation of cardiac failure appeared to increase the probability of CSR by 70 %, increase AHI by 30 events/hr or increase respiratory rate by 25 % in the days or weeks prior to hospitalisation. The results highlight the kinetics of SDB in cardiac failure and the limitations of conventional intermittent review of SDB and cardiac failure. Serial respiratory monitoring may be a mechanism by which patient clinical state can be assessed on an ongoing basis in cardiac failure.

  • (2012) Sims, Andrew Martin
    Thesis
    Obstructive Sleep Apnoea (OSA), characterised by repeated collapse of the pharyngeal airway during sleep, causes cessation of breathing followed by arousal, restoring normality. Continuous Positive Airway Pressure (CPAP) is a non-invasive, effective treatment for OSA where positive pressure is applied to the airway through a mask, maintaining patency. Nasal masks are commonly used, contacting the face across the upper lip, sides of the nose and the nasal bridge. Despite health benefits, therapy compliance is sub-optimal, often due to poor mask fit and discomfort. Masks have been designed to conform to the facial profile, but have not taken into account facial deformations. The nature of facial deformations while undergoing CPAP therapy is unknown. This thesis investigates the contact interactions between the face and a nasal CPAP mask. Magnetic Resonance Imaging (MRI) scans of the face were acquired of participants in the reference configuration and while undergoing CPAP therapy. The CPAP scan volume was registered onto the reference volume prior to surface generation for each state. Perpendicular deformation was measured from the reference facial profile to the deformed profile. Large facial deformations were measured at the sides of the nose (4.6 ± 1.6mm) and the upper lip (4.9 ± 1.8mm) with much smaller deformations at the nasal bridge (2.4 ± 0.2mm). When normalised by applied load and tissue thickness, no difference was found. Finite Element Analysis (FEA) models of the face under CPAP therapy were prepared and validated against experimental data. The explicit FEA method was able to successfully engage the face and mask to simulate the application of CPAP therapy. An indentation study was performed to estimate the mechanical properties of subdermal fat using the Neo Hookean model (μ = 0.53 ± 0.31kPa). A model series was also prepared assuming the face to be rigid. Contact pressures were lower in the deformable models than in the rigid models. A linear association was found between these values at the sides of the nose and at the forehead. These findings and techniques can be used to consider facial deformation in the development of future nasal CPAP masks to improve comfort and compliance to therapy.

  • (2012) Guenther, Thomas
    Thesis
    Electrical stimulation of neural tissue is known to elicit sensations and ac- tuations within the human body. Throughout the last decades, the ability to communicate with neurons was grown and the process become more sophisticated. Todays matured microprocessor technologies and architec- tures allow complex multi-channel stimulation and recording. However, chronic studies of implanted neuroprosthetics comprising hundreds of stim- ulation channels have never been conducted due to the lack of miniaturised encapsulation technologies which can be implanted within the smallest spaces while still withstanding the harsh environment for a long-period of time. In this study, steps towards achieving this goal have been success- fully carried out. Ongoing research was reviewed such that not only the materials, but also their combinations at the joining interfaces are able to withstand decades of implantation. Metallising alumina with platinum was of particular interest due to its established presence in neurostimulators for several decades. In depth knowledge of the bonding mechanism is essential to the understanding of this interface because it a_ects the hermeticity and biocompatibility of the device. Platinum to platinum and titanium to alu- mina interfaces where investigated for structural assembly and long-term stable interconnections. Further studies focused on hermeticity testing of microdevices using helium leak detection. These studies allow to determine possible methods for non-destructive, case-by-case testing to estimate the theoretical life-time of each encapsulation. Microfabrication methods were developed and a design for a neurostimulator encapsulation was outlined to allow the implantation into human body where space constraints are highly restrictive. An illustrative example of the how the above studies can be applied was provided by the complete design-to-prototype development of a visual prosthesis incorporating 98 stimulation channels. The results of testing of the method to miniaturise neuroprosthetic implants indicate advantages of allowing more complex stimulation methods by providing increased numbers of stimulation channels, increased life-time of the im- plants, and miniaturisation to target newly accessible implantation sites.

  • (2012) Ariani, Arni
    Thesis
    One serious issue related to falls among the elderly living at home or in a residential care facility is the ‘long lie’ scenario, which involves being unable to get up from the floor after a fall for 60 minutes or more. The first part of this thesis focuses on developing algorithms for unobtrusive falls detection using simulated responses from passive infrared (PIR) and pressure mat (PM) sensors, aimed at older subjects living alone at home. A Java-based wireless sensor network (WSN) simulator was developed. This simulation reads the room coordinates from a residential map, a path-finding algorithm (A*) simulates the subject’s movement through the residential environment. The fall detection algorithm was tested on 15 scenarios; three scenarios of ADL, and 12 different types of falls (four types of fall, each with three post-fall scenarios). A decision tree-based heuristic classification model is used to analyse the data and differentiate falls events from normal activities. The accuracy of the algorithm is 62.50%. The second part of this thesis focuses on addressing three remaining drawbacks of the previous algorithm and improving the robustness of the system. To solve the problem of the person continuing to move after falling, the potential effectiveness of using two PIR sensors at each location (which monitor the upper and lower halves of the room) is investigated. Graph theory concepts are used to infer how many people (or groups) are present in the environment, loosely track their movement/location, and monitor them independently for falls. This graph representation is also used to identify when someone leaves the residence. A revised fall detection algorithm, also based on a heuristic decision tree classifier model, is tested on 15 scenarios, each including one or more persons; three scenarios of ADL, and 12 different types of falls. The accuracy of the algorithm is 89.33%. Future work will focus on the investigation of the impact of using a more realistic (suboptimal) sensor characteristic on the performance of the designed fall detection algorithm, the fabrication of a hardware prototype and the preliminary implementation of this fall detection system in either a laboratory or real-world environment.

  • (2012) Baek, Sungchul
    Thesis
    A key limitation associated with conducting polymers (CP) for implantable electrode applications is their inferior physico-mechanical properties and the effect of this on biological performance. This research investigates the physico-mechanical cues of conventional conducting polymer coatings and aims to understand their effects on neural adhesion and neurite extension. The underlying hypothesis was that the biological performance of CPs can be effectively controlled by physical cues such as surface topography and mechanical softness. Poly(3,4-ethylenedioxythiophene) (PEDOT) doped with perchlorate, benzenesulfonate, tosylate (pTS), dodecylbenzenesulfonate and polystyrenesulfonate were compared across a range of baseline material properties. Additionally, the deposition charge used to produce PEDOT was varied from 0.05 to 1 C/cm2 to determine an optimal thickness for electrode coatings. To address the need for electroactive biomaterials with improved neural interfacing, nanobrush-CP hybrids were fabricated. Dense poly(2-hydroxyethyl methacrylate) (PHEMA) brushes were grafted via surface-initiated atom transfer radical polymerisation (SI-ATRP). PEDOT/pTS was electrochemically deposited through this nanobrush substrate. The formation of the hybrid was confirmed and characterised across implant performance metrics. The physical, mechanical, electrical and biological performance of PEDOT coatings was used to assess ideal fabrication parameters, optimised for neural cell interactions. Nanoindentation techniques were used to yield the first quantitative values for stiffness moduli of electrodeposited CP coatings on metal substrates. It was found that the nodularity of the CP surface increased with increasing coating thickness and decreasing dopant size. A major finding of this study was that high roughness of conventionally doped PEDOT produced on the micron scale, prevented attachment of neural cells. Consequently, thin PEDOT films doped with the low toxicity anion, pTS, supported the greatest cell attachment and neurite outgrowth. Electrochemical performance was analyzed and supported the finding that thin PEDOT/pTS provides significant biological and electrochemical advantages over platinum electrodes. The nanobrush/CP hybrid further improved the electrochemical properties of conventional CPs and offers a new approach for selective cell attachment via the CP coated region of the brush substrate. This thesis demonstrates that the biological performance of CPs is strongly influenced by the physico-mechanical properties with optimal coatings produced in the sub-micron range using conventional doping ions. A new hybrid nanobrush/CP is presented with fabrication parameters which can be tailored for target material properties. Future work will focus on delineating the interfacial structure of the hybrid to optimise the cushioning effect of the brushes for neural interface applications.

  • (2012) Mohktar, Mas Sahidayana
    Thesis
    The increasing use of telehealth technologies to remotely monitor patients with chronic obstructive pulmonary disease (COPD) has enabled pre-emptive management of these patients by clinical teams. However, the altered monitoring workload imposed on the clinical care team associated with using a telehealth management strategy has been given less attention. This thesis describes the design of a decision support system (DSS) to assist clinical care teams in managing COPD patients. The development of an overall DSS framework for a prospective application is firstly described. An analysis of home telehealth data contained in retrospective databases is used to develop the DSS’s knowledge base (rules engine) to facilitate COPD management. Moreover, a preliminary exploration of the effect of data quality on DSS operation is also presented. The proposed DSS design was implemented using a business process management system with a rules engine as the core component. The objective of the rules engine is to assist the clinical team with the detection of possible COPD exacerbation events, thus facilitating referral decisions. The rules were constructed with two separate clinical measurement databases (termed Database I and Database II); collected from COPD patients enrolled in home telehealth intervention groups as part of two randomised controlled trials. The data were pre-processed and features were extracted, then a classification and regression tree (CART) technique was used to generate the rules. Four types of CARTs were constructed using four different reference standards, two from each database. The accuracies of the COPD exacerbation algorithms were 79.00% and 76.72%, and the referral recommendation CARTs kappa values were 0.52 and 0.45, for Database I and Database II, respectively. The results showed that the CARTs constructed using home telehealth data were capable of detecting COPD exacerbations as well as generating referral recommendations. In addition, data quality analysis that was performed on the data used by one of the CART algorithms confirmed that data quality issues did affect the reliability of the particular algorithm. In summary, this thesis presents a DSS that specifically could be used to facilitate the remote monitoring and management of COPD patients. More generally it helps inform how similar DSSs linked to telehealth systems could improve the management of patients suffering chronic disease.

  • (2012) Yin, Shijie
    Thesis
    The loss of vision through degenerative retinal diseases is a tragic human condition affecting millions around the world. Development of a visual prosthetic device hoping to restore vision to these patients is underway by electrically stimulating the retinal ganglion cells of the retina with nearby electrodes. These neurons responsible for the transmission of electrical signals to the visual cortex of the brain are thought to be largely intact even in patients who have been blind for many years. The pursuit of eliciting useful vision faces a great number of challenges in both device design and stimulation strategy. Powerful tools such as mathematical models can assist by redirecting the focus of implant and stimulus algorithm design to critical areas. Previous retinal models primarily focused on either a compartmental approach employing active descriptions of cellular membrane mechanisms or discrete network models. However, the extent of spatial activation of the retina on a large scale is not considered, nor are the effects of the network in shaping spiking activity taken into account in a continuum sense. The development of a novel pseudo-bidomain model incorporating presynaptic inputs from deeper retinal neurons will be presented in this thesis. Model parameters are tuned to reflect feasible responses to epiretinal stimulation and validated against suprachoroidal stimulation and various electrode and stimulus configurations. Simulation findings suggest a threshold charge density for activation of 50 ± 2 µC/cm2 for epiretinal stimulation with a disc electrode of 200 µm radius and a rectangular cathodic stimulus of 100 µs pulse width. For suprachoroidal stimulation, this was observed to be 137 ± 2 µC/cm2. Inclusion of presynaptic inputs elicited stimulus-locked and network driven action potentials. For epiretinal stimulation presence of early and late onset action potentials were observed with latencies of 0.3 and 7 ms respectively with a charge density of 398 - 438 µC/cm2. In comparison suprachoroidal stimulation displayed an earlier network driven response (6.4 ms) at a lower charge density of 223 - 231 µC/cm2. These near threshold and latency findings were consistent with published works and present a novel approach to examining retinal activation in a spatiotemporal setting.

  • (2012) Bai, Siwei
    Thesis
    Electroconvulsive therapy (ECT) and transcranial direct current stimulation (tDCS) are two important forms of transcranial electrical stimulation in clinical psychiatry. They have shown impressive therapeutic results in the treatment of major depression and other psychiatric disorders. The aim of this thesis was to develop novel computational models of ECT and tDCS to assist in the further understanding of these two brain-stimulation techniques, to explore possible refinements and improvements in treatment efficacy. Head models of three different subjects were reconstructed from corresponding computed tomography (CT) or magnetic resonance imaging (MRI) scans. One was a low-resolution model rendered from a set of CT scans, incorporating skull conductivity anisotropy. The other two were high-resolution models reconstructed from MRI scans, with one incorporating white matter conductivity anisotropy. In both high-resolution models, several brain cortical regions of interest were segmented and defined; these are known to be involved in therapeutic or adverse stimulation outcomes. In one set of simulations, these structural head models were taken to be passive volume conductors, to investigate the effect of various electrode montages on the distribution of current density or electric field within the head. Results showed that current distribution in the brain was highly dependent on the electrode placement on the scalp. For example, when simulating three different right unilateral (RUL) ECT montages, the non-conventional montages with an electrode on the forehead appeared to have superiority over conventional RUL, because stimulation strength was stronger in regions believed responsible for the treatment efficacy, such as the anterior cingulate gyrus, and was weaker in regions that have been speculated to exert adverse effects, such as the hippocampus. In addition, a continuum active model of neural excitation was also developed to simulate direct activation of the brain following an ECT stimulus. This model was integrated into the passive head model to investigate the influence of different electrode placements, as well as the time-dependent effects of ECT stimulus parameters on brain activation. For instance, when the stimulus pulse width was reduced, maximum current density was unchanged but the spatial extent of activation was reduced. Moreover, results showed that stimulus frequency influenced the stimulus efficiency, that is, of all the brain neurons that were able to be directly activated by a single pulse, 80%, 10% and 0% were capable of being activated by both of two consecutive pulses with frequencies of 60 Hz, 90 Hz and 120 Hz, respectively.