The aim of this thesis was to develop biodegradable devices loaded with chemotherapy drug. The system is targeted for advanced ovarian cancer treatment through the intraperitoneal (IP) route of administration. Polylactide-co-glycolide (PLGA) was selected as the model biodegradable polymer to produce drug-loaded microsphere, hollow and solid fibres. Copolymer PLGA with three different lactic:glycolic acids ratios; 50:50, 65:35 and 75:25 were used in order to compare their drug loading capacities and in vitro drug release profiles. Cisplatin, a cytotoxic drug with proven activity against ovarian cancer was selected as the model chemotherapy drug. Intraperitoneal administration is often associated with abdominal pain therefore a local anaesthetic, lidocaine, was selected for the purpose of pain relief.

Brachytherapy refers to the therapeutic use of encapsulated radionuclides within or close to a tumor. Today brachytherapy is used as an alternative to surgery or beam therapy to treat different kinds of cancers such as breast, lung, prostate, ovarian and pancreatic, primary and metastatic hepatic tumors and rheumatoid arthritis. Microspheres are one therapy utilized in brachytherapy procedures. Despite the development of advanced equipment and methods, there is still a limited knowledge of radiation dose distribution when utilizing this technique. This study focuses on random packing of microspheres and seeks to determine dose distributions for specific cases. The Monte Carlo Neutral Particle code (MCNP) developed by Los Alamos National Laboratory is used to simulate beta particle transport. Pr-142 is the beta source utilized for all calculations. The cylinder radii are 0.1, 0.15 and 0.3 cm and sphere radii are 0.03, 0.05 and 0.07 cm. The results are verified by examining limiting cases: uniformly distributed source and line of microspheres. Based on the data collected, the correlations between the average dose, its related variance, and distance from the cylinder were determined. An approach for estimating the surface average dose was developed and suggestions regarding an approach to assess surface variance estimation were presented.

This thesis presents the development of a refractometric sensor based on quantum dot-embedded polystyrene microspheres. The technique uses optical resonances within a microsphere, known as Whispering-Gallery Modes (WGMs), which produce narrow spectral peaks. The basic theory of WGMs is reviewed and specifically discussed for biosensing application. The spectral shifts of WGM peaks are sensitive to changes in the local refractive index. In the experiments, two-photon excited luminescence from the quantum dots couples into several WGMs within the microresonator. By optimizing the detection area, the spectral visibility of the WGMs is improved. The spectral shifts are measured as the surrounding index of refraction changes. The experimental sensitivity is about five times greater than that predicted by Mie theory. The sensor element is based on commercially available dielectric microspheres with a diameter about 10 μm. Thus, the technique is more economic and suitable for sensing applications, compared to microspheres of 100 μm in size which can only be made in the laboratory.

Intrapulmonary arteriovenous anastomoses (IPAVA) are vascular conduits through which blood flow bypasses the pulmonary circulation, and does not participate in pulmonary gas exchange. Blood flow through IPAVA (QIPAVA) is known to increase with increasing cardiac output, such as exercise, and while breathing normobaric, hypoxic gas at rest or during exercise. Previous studies demonstrate that QIPAVA is decreased at rest and during exercise in hypobaria compared to equivalent normobaric conditions. Studies involving postural changes have shown that QIPAVA may change with body position. In human studies, QIPAVA is measured either by transthoracic saline contrast echocardiography (TTSCE) or by injection of 99mTc-labeled macroaggregates of albumin (99mTc-MAA). It is unknown if discrepancies in measuring QIPAVA in normobaria and hypobaria, and in different body positions, represent real physiological changes or if they are methodological artifacts. In Chapter IV, the effect of hypobaria on QIPAVA was investigated. QIPAVA was reduced during exercise in hypobaria in normoxia and hypoxia compared to normobaric conditions, however gas exchange efficiency was unimpaired. This suggests that pulmonary blood flow may change in hypobaria such that blood flow is directed away from IPAVA. Alternatively, it may suggest that saline contrast is less stable at high altitude and not detected by TTSCE. In Chapter V, the effect of changing body position on QIPAVA as detected by TTSCE was investigated in human subjects at rest. No significant changes were observed in QIPAVA with postural changes. In Chapter VI, a perfusion model was used to investigate behavior of saline contrast microbubbles, MAA, and microspheres (20 µm and 50 µm diameter) encountering a vertical bifurcation. The results indicated that microbubbles and 20 µm microspheres tend to enter the upper branch of the bifurcation, whereas MAA and 50 µm microspheres tend to enter the lower branch. In Chapter VII, the effect of atmospheric pressure on the initial microbubble radius (Ro) of agitated saline contrast microbubbles was investigated. The results of this study demonstrated that the Ro of microbubbles created at sea level pressure was significantly smaller than Ro of microbubbles created at higher altitudes (1,668 m and 5,260 m). / 2019-01-09

<p>In this thesis, a study of the rational design and fabrication of microfluidic systems for microsphere generation is presented. The required function of microfluidic systems is to produce microspheres with the following attributes: (i) the microsphere size being around one micron or less, (ii) the size uniformity (in particular coefficient of variation (CV)) being less than 5%, and (iii) the size range being adjustable as widely as possible.</p> <p>Micro-electro-mechanical system (MEMS) technology, largely referring to various micro-fabrication techniques in the context of this thesis, has been applied for decades to develop microfluidic systems that can fulfill the foregoing required function of microsphere generation; however, this goal has yet to be achieved. To change this situation was a motivation of the study presented in this thesis.</p> <p>The philosophy behind this study stands on combining an effective design theory and methodology called Axiomatic Design Theory (ADT) with advanced micro-fabrication techniques for the microfluidic systems development. Both theoretical developments and experimental validations were carried out in this study. Consequently, the study has led to the following conclusions: (i) Existing micro-fluidic systems are coupled designs according to ADT, which is responsible for a limited achievement of the required function; (ii) Existing micro-fabrication techniques, especially for pattern transfer, have difficulty in producing a typical feature of micro-fluidic systems - that is, a large overall size (~ mm) of the device but a small channel size (~nm); and (iii) Contemporary micro-fabrication techniques to the silicon-based microfluidic system may have reached a size limit for microspheres, i.e., ~1 micron.</p> <p>Through this study, the following contributions to the field of the microfluidic system technology have been made: (i) Producing three rational designs of microfluidic systems, device 1 (perforated silicon membrane), device 2 (integration of hydrodynamic flow focusing and crossflow principles), and device 3 (liquid chopper using a piezoelectric actuator), with each having a distinct advantage over the others and together having achieved the requirements, size uniformity (CV ⤠5%) and size controllability (1-186 &#x00B5;m); (ii) Proposing a new pattern transfer technique which combines a photolithography process with a direct writing lithography process (e.g., focused ion beam process); (iii) Proposing a decoupled design principle for micro-fluidic systems, which is effective in improving microfluidic systems for microsphere generation and is likely applicable to microfluidic systems for other applications; and (iv) Developing the mathematical models for the foregoing three devices, which can be used to further optimize the design and the microsphere generation process.</p>

Thalassemia, a genetic blood disorder, occurs as a result of deformations of hemoglobin structures. Patients with thalassemia develop iron overload from chronic blood transfusions and require regular iron chelation to prevent potentially fatal iron-related complications. Deferiprone is a commercially available drug used as iron chelator for the treatment of thalassemia but the very long-term effectiveness is not clearly known yet. Therefore, some studies were carried out to find effective alternative drugs or delivery methods for treatment of thalassemia. Controlled delivery, which offers safer, more convenient, and more effective means of administering actives, seems promising with this respect. Chitosan, a natural biopolymer produced from deacetylation of chitin, has a variety of promising pharmaceutical uses and is presently considered as a novel carrier material in drug delivery systems. In this study, chitosan microspheres having different degree of deacetylation (DDA) and containing Deferiprone were prepared by oil/water emulsion method and by crosslinking with gluteraldehyde. Particle size, SEM, and in vitro drug release analysis were performed. The average sizes of the prepared microspheres increased with increasing degree of deacetylation of chitosan and with decreasing crosslinking degree. In vitro drug release studies showed that, the release rate of Deferiprone increased as the crosslinking degree increased, contrary to the expectations. This is explained by the crystalline structure of lightly crosslinked chitosan which have ordered and dense structure causing slower release rate for Deferiprone compare to highly crosslinked structures. In the second stage of the study, chitosan films hardened with gluteraldehyde were prepared by film casting method. IR, DSC and mechanical analysis were performed. For the films with various crosslinking degrees, it was found that UTS values differed from 50.6 MPa to 102.7 MPa, mean elastic modulus values differed from 3328.7 MPa to 3790.1 MPa and SAB values differed from 2.06% to 4.29%.

<p>In this thesis, a study of the rational design and fabrication of microfluidic systems for microsphere generation is presented. The required function of microfluidic systems is to produce microspheres with the following attributes: (i) the microsphere size being around one micron or less, (ii) the size uniformity (in particular coefficient of variation (CV)) being less than 5%, and (iii) the size range being adjustable as widely as possible.</p> <p>Micro-electro-mechanical system (MEMS) technology, largely referring to various micro-fabrication techniques in the context of this thesis, has been applied for decades to develop microfluidic systems that can fulfill the foregoing required function of microsphere generation; however, this goal has yet to be achieved. To change this situation was a motivation of the study presented in this thesis.</p> <p>The philosophy behind this study stands on combining an effective design theory and methodology called Axiomatic Design Theory (ADT) with advanced micro-fabrication techniques for the microfluidic systems development. Both theoretical developments and experimental validations were carried out in this study. Consequently, the study has led to the following conclusions: (i) Existing micro-fluidic systems are coupled designs according to ADT, which is responsible for a limited achievement of the required function; (ii) Existing micro-fabrication techniques, especially for pattern transfer, have difficulty in producing a typical feature of micro-fluidic systems - that is, a large overall size (~ mm) of the device but a small channel size (~nm); and (iii) Contemporary micro-fabrication techniques to the silicon-based microfluidic system may have reached a size limit for microspheres, i.e., ~1 micron.</p> <p>Through this study, the following contributions to the field of the microfluidic system technology have been made: (i) Producing three rational designs of microfluidic systems, device 1 (perforated silicon membrane), device 2 (integration of hydrodynamic flow focusing and crossflow principles), and device 3 (liquid chopper using a piezoelectric actuator), with each having a distinct advantage over the others and together having achieved the requirements, size uniformity (CV ⤠5%) and size controllability (1-186 &#x00B5;m); (ii) Proposing a new pattern transfer technique which combines a photolithography process with a direct writing lithography process (e.g., focused ion beam process); (iii) Proposing a decoupled design principle for micro-fluidic systems, which is effective in improving microfluidic systems for microsphere generation and is likely applicable to microfluidic systems for other applications; and (iv) Developing the mathematical models for the foregoing three devices, which can be used to further optimize the design and the microsphere generation process.</p>

This thesis covers the construction and characterisation of microlasers based on whispering gallery modes in ytterbium-doped microsphere resonators. The microlasers were made by drawing and fusing Yb-doped silica optical fibre into microspheres of approximately 100 μmin diameter using CO2 laser-induced melting. Access to whispering gallery modes was accomplished using a prism coupled to the evanescent field of the internal cavity modes. Microspheres with Q-factors of up to 10^7 were made using this technique. CW multimode lasing was observed at 1050 nm, with a pump threshold required for lasing estimated to be of the order of 100 μW for a 900 nm pump. Both TE and TM modes were identified in the laser emission and the ability to selectively excite each mode family (TE or TM) is shown to be directly controlled by the pump. Pulsed lasing was also observed at 975 nm and 1050 nm.

abstract: The purpose of this study was to determine the applicability of fluorescent microspheres as a surrogate to measure the removal of Cryptosporidium oocysts through the coagulation, flocculation, sedimentation, and filtration steps of conventional water treatment. In order to maintain accuracy and applicability, a local water treatment facility was chosen as the system to model. The city of Chandler Arizona utilizes conventional treatment methodologies to remove pathogens from municipal drinking water and thus the water, coagulant, polymer, and doses concentrations were sourced directly from the plant. Jar testing was performed on four combinations of coagulant, polymer, and fluorescent microsphere to determine if the log removal was similar to that of Cryptosporidium oocysts. Complications with the material properties of the microspheres arose during testing that ultimately yielded unfavorable but conclusive results. Log removal of microspheres did not increase with added coagulant in the predicted manner, though the beads were seen aggregating, the low density of the particles made the sedimentation step inefficient. This result can be explained by the low density of the microspheres as well as the potential presence of residual coagulant present in the system. Given the unfavorable properties of the beads, they do not appear to be a suitable candidate for the surrogacy of Cryptosporidium oocysts in conventional drinking water treatment. The beads in their current state are not an adequate surrogate; however, future testing has been outlined to modify the experiment in such a way that the microspheres should behave like oocysts in terms of physical transportation. / Dissertation/Thesis / Masters Thesis Civil Engineering 2015

Master of Science in Biomedical Sciences / Department of Clinical Sciences / Elizabeth G. Davis / To protect horses from disease, equine practitioners typically prescribe a protocol of an initial primary vaccination followed by a booster vaccination 3-4 weeks later. Subsequent boosters are given every 6-12 months depending on the pathogen of concern. Each vaccination incurs an additional cost and increased chance for adverse reactions. Despite wide-spread protocol acceptance, duration of effectiveness of vaccines in protecting horses from disease is not well documented. It was hypothesized that horses vaccinated annually since birth have increased antibody production that remains consistent and sufficient for long-term protection from common diseases. This work resulted in the development of a novel, multiplex-magnetic bead-based indirect immunoassay to screen sera from vaccinated adult horses to measure antibody levels in response to vaccine administration. Antigens tested included West Nile Virus, Eastern Equine Encephalitis, Western Equine Encephalitis, Equine Influenza Virus, Equine Herpes Virus 1 and 4, Tetanus, and 7 different Rabies antigens (3 lab and 4 wild strains). The developed assay was a 7-plex capture antibody, which quantified equine IgG (Immunoglobulin G) that binds viral antigens derived from different rabies virus strains along with pure vaccine samples of the 7 different antigens. A 7-point standard curve was developed to quantify the viral-antigen reactive IgG concentration in vaccinated horse serum. Vaccinated horses increased serum antibody concentration for each antigen post-vaccination with the percent increase ranging between 34.0% for Equine Herpes Virus 4 and 257.3% for Equine Influenza Virus. Use of the novel assay will provide equine veterinarians with an economical method to measure immune activation toward common pathogens of concern. This methodology will provide foundation level information regarding antigen specific IgG concentrations that ultimately may be extrapolated to establish protective levels of immunity resulting in establishment of vaccine protocols.