1.   Sammanfattning Introduktion: Det finns idag flera allvarliga infektioner som har utmanande farmakologisk behandling, där tuberkulos är en av dem. Patogenerna som orsakar tuberkulos är svåra att behandla på grund av deras resistensmekanism, vilket gör att antibiotika inte fungerar lika effektivt längre som de gjorde tidigare. Ett sätt att studera nya antibiotika är att använda hollow fiber modellen. Hollow fiber modellen är en metod som utnyttjar en kassett med semipermeabla filter som tillåter att antibiotikumet fluktuerar i systemet, vilket ska efterlikna människokroppens plasmakoncentration. Detta är ett mer anpassat system jämfört med konventionella in vitro studier som undersöker konstanta koncentrationer i plasma, för att hollow fiber modellen visar effekten vid fluktuerande koncentrationer. Syfte: Syftet med studien var att hitta tillgänglig information om hollow fiber systemet, vilka studier som har gjorts och hur man kan modifiera systemets egenskaper, som pumphastigheter och antal flaskor, för att efterlikna farmakokinetiken i kroppen på ett optimalt sätt. Metod: Studien är en litteraturöversikt som använt sig av Pubmed och Web of Science Core Collection för att samla in vetenskapliga artiklar. Ett urvalssystem har använts för att samla in artiklar som är relevanta till syftet och sökord som använts var ”hollow fiber”, ”HFS”, ”in vitro” och ”tuberculosis”. Inklusionskriterier var artiklar på engelska och maximalt fem år gamla och exklusionskriterier var studier som inte använde sig av hollow fiber systemet för att studera bakterier som patogener. Förutom insamling av data från vetenskapliga artiklar utfördes en intervju med två experimentalister inom området hollow fiber infektionsmodellen. Resultat och diskussion: Baserat på studierna används hollow fiber modellen för att undersöka 1) läkemedelskombinationer, 2) bakterieresistens och 3) hur PD beror på PK-parametrar. Parametrar som behövs vid studien är Cmax, Cmin, tmax, halveringstid, clearance och AUC (farmakokinetiska), som resulterar i TTP, CFU, MIC, EC50 och Emax (farmakodynamiska). Beroende på typ av läkemedel anpassas de olika farmakokinetiska modellerna till systemet och därför krävs ibland en kombination av pumpar och flödeshastigheter, speciellt om flera läkemedel ska testas eller ifall läkemedlet följer mer komplex farmakokinetisk distribution och elimination än one-compartment kinetik. Systemet kan även modifieras så att den kan efterlikna absorptionsfasen ifall läkemedlet ska konstrueras till en peroral administrering (tablett, kapsel, oral lösning).  Slutsats: Hollow fiber systemet har använts för att undersöka antibiotikas bakteriedödande effekt. Olika farmakokinetiska modeller kan anpassas till systemet för att efterlikna den avdödande effekten i kroppen, genom att ändra antal flaskor, pumpar och flödeshastigheterna i pumpinställningarna.

No description available.

No description available.

Hollow fiber membranes (HFMs) formed through phase inversion methods exhibit specific physicochemical characteristics and generally favorable surface and mechanical properties, supporting their use in diverse applications including ultrafiltration, dialysis, cell culture, bioreactors, and tissue engineering. Characterization of, and modifications to, such membranes are important steps in achieving desired characteristics for specific applications. HFMs subject to gas, irradiation, and chemical sterilization techniques were characterized based on several analytical techniques. It was revealed that these common sterilization techniques can cause inadvertent changes to HFM properties. While these changes may cause detrimental effects to HFMs used in filtration, the methods of sterilization are also presented as a facile means of tuning properties toward specific applications. Modifications to HFM surface chemistries were also sought as a method of adsorbing bacterial lipopolysaccharide (LPS) from solutions used in hemodialysis treatments and bioprocessing applications. It was found that additives such as polyvinylpyrrolidone (PVP), polyethyleneglycol (PEG), and poly-L-lysine (PLL) can facilitate adsorption capacities of HFMs toward LPS. Additionally, chemical changes are presented as a means of preferentially adsorbing LPS to specific locations on the HFM surface.

Electrically conductive membranes (ECMs) are of significant research interest for their ability to mitigate fouling, enhance separation capacity, and induce electrochemical degradation of contaminants. Most ECM development has been in flat sheet format suitable for laboratory studies; in industrial applications, formats such as hollow fiber (HF) are preferred for their high packing density. While ECMs in HF format are emerging in research, these techniques typically employ the same methods proven for flat sheet, often involving direct deposition of conductive material onto a support membrane with no further investigation into how the deposition process affects ECM properties. This is a significant challenge for long (~1 m) HF membranes where coating uniformity is essential to ensure consistent performance. The goal of this project was to fabricate conductive HF membranes, ensuring uniform performance along the fiber. In this work, we have developed a “crossflow deposition” technique to deposit a uniform layer of single walled/ double walled carbon nanotubes (SW/DWCNTs) onto the interior surface of commercial polyether sulfone HF membranes. In a design-of-experiments model, feed pressure and crossflow velocity were shown to directly impact composite membrane conductivity and permeability. The highest permeability (~2900 LMH/bar) and conductivity (~670 S/m) were both achieved at the high pressure (0.2 bar) and high crossflow velocity (1.06 cm/s) condition. An inverse relationship was identified between conductivity and permeability for 29 different HF membranes coated under various flow and particle loading conditions. Similar trends were evident in ECM literature when comparing 80 membranes across 38 papers, covering various conductive materials, separation types, configurations, and applications. Metallic-based ECMs outperformed graphitic nanomaterial or conductive polymer-based ECMs with conductivities three orders of magnitude higher. This review also revealed a wide variation in performance testing with 35 unique pollutants in 63 total tests, indicating a need for standardization to accurately compare ECMs and a need for testing with more realistic feed sources. Finally, electrochemical degradation of methyl orange using the CNT-coated HF membranes was evaluated in batch and continuous removal experiments. Although no significant MO removal was detected in either configuration, these modules can be used for further optimization in terms of targeted conductivity, contact time, and electrochemical parameters such as applied voltage. This work highlights the existence of a conductivity/ permeability trade-off in ECM development and how manipulation of flow parameters during deposition can impact this trade-off in HF membrane development. / Thesis / Master of Applied Science (MASc) / Membrane separation technologies are a common purification strategy in many fields due to their simplicity and low energy requirements. Membranes operate by rejecting particles from feed water based on their chemical or physical properties such as size or charge. Long-term membrane operations are limited by fouling, incurring large operating costs for frequent cleaning cycles and downtime. Furthermore, traditional membrane separations only physically remove particles, presenting a risk for contaminant re-introduction into the environment. Electrically conductive membranes are an emerging strategy for addressing these concerns due to their demonstrated antifouling, enhanced selectivity, and redox capabilities. To date, these membranes have almost exclusively been developed as flat sheets with limited research into other membrane formats. Hollow fiber membranes resemble thin tubes ~1 mm in diameter and up to ~1 m in length where filtration occurs through the tubular wall of the fiber; the small diameter allows for hundreds of fibers to pack into an individual module, thus maximizing throughput. In this thesis, several issues with hollow fiber conductive membrane fabrication are addressed to ensure consistent performance along the length of the fiber. A key trade-off between membrane surface conductivity and throughput was found to exist universally in the conductive membrane field. This knowledge can be used to select fabrication methods and parameters to target certain performance ranges.

No description available.

No description available.

No description available.

No description available.

<p>Sample preparation is a crucial processing step required for molecular biological analysis of environmental samples like water that has a variety of constituents in it. Furthermore, large volumes of sample need to be processed as the prescribed limits of pathogens in water are extremely low. However, microfluidic biosensing devices that can perform rapid molecular biological analysis in the field are designed to handle small sample volumes. In such cases, there is a need for a sample processing device that can reduce (concentrate) a large sample volume into a small one while retaining the biological species present in it. Hollow fibers are appropriate for this purpose of sample reduction and serve as a macro to micro interface for the microfluidic device. The received concentrate from the hollow fiber device requires be further concentrated to several microliters and separated and sorted to various modular components within the microfluidic device. This requires a second stage microfiltration where an integrated membrane can sort based on particulate size. In this thesis, a two stage filtration was designed. A first stage hollow based fiber pre-concentration device is developed that is portable, low cost, has high retention efficiency, low elution volume and is rapid. The hollow fiber device has low elution volume of ~1-3 ml. Controlled experiments were performed to validate the recovery of the hollow fiber device. Simulated 250 ml E.coli contaminated samples were filtered to <5 ml from an original sample volume of 250 ml. No bacteria were present in the filtrate and nearly 100% was recovered at high bacterial concentrations. At low concentrations (~200 cells in the sample) the recovery was less (~50%). A second stage microfiltration device that can be integrated with the microfluidic device and that can reduce the sample still further from ~ 5 ml to 5 μl was designed. Plasma bonding of ultrafiltration and microfiltration membranes using fluorine ions was investigated for fabrication of this device. The bonding of PDMS channels with polysulfone membranes via SF6 plasma was tested via tensile pull tests, burst pressure tests, and analyzed through scanning electron microscopy and electron dispersive x-ray spectroscopy. Quantitative tests on 10kDa and 70kDa polyethersulfone membranes demonstrated increased operational bonding strength of 86.6 and 146.9 kPa increases with three hour plasma application. Microfiltration membranes (0.2 micrometer pore size polyethersulfone) bonded in such a way that was easier to permeate as compared to ultrafiltration membranes. This bonding technique is generic in nature and can be used for integration of other commercially available polyethersulfone membranes with microfluidic devices for applications such as bio separations. No filtration testing was performed with E.coli samples.</p> / Master of Applied Science (MASc)