Design and development / Respiratory distress syndrome (RDS) is a major cause of mortality and long-term morbidity annually affecting 14% preterm infants worldwide. Therapies have been developed to overcome this common disorder; however, limitations exist with these treatments that often lead to complications including bronchopulmonary dysplasia (BPD). One approach to address RDS is to implement a microfluidic oxygenator that serves as a respiratory support system for preterm neonates while the lungs fully develop, extra-uterine. This artificial lung assist device (LAD) is characterised by its non-invasiveness (given that it is connected via umbilical vessels), pumpless configuration, ambient air operation, portability and low priming volume. Furthermore, the LAD is formed by single oxygenator units (SOU) that are stacked in a parallel array which allows for usage on different body weights. The objective of this thesis is to design an electrochemical system to provide an in-situ enriched O2 environment able to supply 1.9 ml O2/min for use in the SOU while maintaining the simplicity of operation of the oxygenator. An inexpensive, electrically powered and compact device was envisioned allowing for a higher permeation flux to fully oxygenate the blood. Moreover, the system would be easy to manufacture, low maintenance and avoid the risk of gas contamination. In the initial work, different designs of electrolytic cells were developed and tested. The two- chamber design connected by a gel membrane showed an O2 production 10 times higher than with previous designs with 42 mg O2/L. Subsequently, different supporting electrolytes were tested. NaOH demonstrated a better performance and no degradation of the electrode in contrast to NaCl and Na2SO4. Stainless steel mesh (SSM) and graphite sheet electrodes were then tested; it was observed that stainless steel produced 3.4 times more dissolved oxygen (DO) than graphite with 28.3 mg O2/L. Experimentation with electrolysis of water showed that the DO in water reached stability 3 min after the electrolysis process was initiated measuring a change of DO of 29 mg/L at 3 A. Furthermore, an active oxygenation (AO) system was developed for in-vitro experiments via electrolysis of water and compared to a passive oxygenation (PO) system exposing blood to enriched O2 air and ambient air, respectively. It was demonstrated that AO provided 300% greater oxygenation to blood than PO. The electrolysis chamber designed for the microfluidic oxygenator allows the oxygenator to maintain its essential characteristics of simplicity and low cost while increasing the rate of oxygenation of blood. Preterm neonates suffering from RDS need an artificial lung that can partially support the oxygenation of their blood. Thus, combining the oxygenator with the O2 generation in-situ system enables a greater blood O2 uptake of 300% making possible the development of an efficient artificial lung. / Thesis / Master of Applied Science (MASc)

Photodynamic therapy (PDT) is a form of local cancer treatment in which cell death is caused by photochemical reactions involving an exogenous photosensitizer. The photosensitizer, which is preferentially retained in malignant tissues, is photoactivated and cell death results from the generation of reactive products -most likely excited molecular (singlet) oxygen. The development of in vivo PDT dosimetry would be greatly aided by the ability to directly measure the local concentration of this product by non-invasive means. In condensed media singlet oxygen will, with some small probability, undergo a radiative transition to the ground state with emission at 1270 nm. This infrared phosphorescence may provide a means for monitoring the production of singlet oxygen in vivo. Unfortunately the background infrared fluorescence observed from tissue may be many times the expected magnitude of the 1270 nm phosphorescence, even within the bandwidth encompassing the peak. The principal aim of this project was the design of a system optimized for the in vivo detection of the singlet oxygen emission. The system makes use of the most sensitive commercially available detector and uses phase sensitive detection to discriminate against infrared fluorescence. The system's performance matched theoretical expectations for the photosensitizer Photofrin II in aqueous and methanol solutions. However, a discrepancy in the observed and theoretical values was noted for aluminum chlorosulphonated phthalocyanine suggesting a deviation from simple first order kinetics. Singlet oxygen phosphorescence was not observed during PDT of cell suspensions or mouse tumours even though considerable cell death and tumour necrosis were observed. The most likely explanation of this failure is that, due to quenching by biomolecules, the lifetime of singlet oxygen in cells or tissue is much lower than in solution so that the probability of emission is reduced accordingly. Quantitative calibration of the system yielded a lower limit of approximately 0.1 us on the singlet oxygen lifetime in tissue. This suggests that singlet oxygen is generated in a protein environment. / Thesis / Master of Science (MS)