Återvinning av litiumjonbatterier (LIB) är avgörande på grund av kritiska råmaterialreserver och miljöhänsyn vid kassering. Hydrometallurgisk LIB-återvinning, en framstående industriell teknik, står inför kostnadseffektivitets- och komplexitetsutmaningar. Samtidig kristallisering visar lovande för effektivisering av återvinning genom att extrahera föreningar från förbrukad batterilut med flera komponenter, vilket kräver hög renhet och effektiv kristallseparation. Detta innebär emellertid att man förhindrar oönskade polykristallina partiklar och samkristaller.Kristallisering är vanligt vid LIB-återvinning, men vanligtvis från enkomponentlösningar för att undvika föroreningar. Kärnbildningskontroll, särskilt i flerkomponentlösningar, är fortfarande utmanande, vilket påverkar industriell effektivitet. Sådd, en vanlig kontrollmetod, inducerar ofta oavsiktliga polykristallina partiklar och vätskeinneslutningar, som understuderas på grund av experimentella begränsningar. Microfluidics erbjuder ett värdefullt verktyg för att studera kristallisationskinetik, växla från utrustningsbaserad till prediktiv fysikalisk-kemisk design. Förbättrad blandning och värmeväxling gör den idealisk för kärnbildningsforskning under kristallisation. Denna avhandling fokuserar på avgörande aspekter av samtidig kristallisation. Huvudsyftet är att utveckla en optimerad mikrofluidisk design och simulera mikrofluidikkanalen för att bestämma initiala processparametrar för experiment samt att få det mest förutsägbara området för kristallbildning inom mikrofluidik. Utmaningar i de mikrofluidiska kristallisationssystemen, såsom kanalblockering, som lätt kan uppstå på grund av kristallbildning eller agglomerationer, har tyvärr begränsat de experimentella resultaten. Icke desto mindre kommer denna avhandling att stödja ytterligare experiment med mikrofluidikanordningen under mikroskopi som kommer att hjälpa till att övervinna dessa utmaningar. Arbete med att minska begränsningarna i denna avhandling kan hjälpa till att förstå multikomponentkristallisationen i realtid och faktiskt den nödvändiga uppställningen och infrastrukturen för mikrofluidikexperiment och i förlängningen bidra till att minska de hydrometallurgiska stegen i komplex metallåtervinning. Därför bidrar det till att främja områdena batteriåtervinning, mikrofluidik och samtidig kristallisering. / Recycling lithium-ion batteries (LIB) is essential due to critical raw material reserves and environmental concerns during disposal. Hydrometallurgical LIB recycling, a prominent industrial technology, faces cost-efficiency and complexity challenges. Simultaneous crystallization shows promise for streamlining recycling by extracting compounds from multicomponent spent battery liquor, demanding high purity and effective crystal separation. However, this entails preventing unwanted polycrystalline particles and cocrystals. Crystallization is common in LIB recycling, but usually from single-component solutions to avoid impurities. Nucleation control, especially in multicomponent solutions, remains challenging, affecting industrial efficiency. Seeding, a common control method, often induces unintended polycrystalline particles and fluid inclusions, which are understudied due to experimental limitations. Microfluidics offers a valuable tool for studying crystallization kinetics, shifting from equipment-based to predictive physical-chemical design. Enhanced mixing and heat exchange make it ideal for nucleation research during crystallization. This thesis focuses on crucial aspects of simultaneous crystallization. The main objective is to develop an optimized microfluidic design and simulate the microfluidic channel to determine initial process parameters for experimentation as well as to get the most predictable region of crystal formation within microfluidics. Challenges in the microfluidic crystallization systems, such as channel blockage, which can easily occur due to crystal formation or agglomerations, have unfortunately limited the experimental results. Nonetheless, this thesis will support the further experimentation of the microfluidics device under microscopy which will help to overcome these challenges. Work on reducing the limitations of this thesis can assist in understanding the multicomponent crystallization in real-time and indeed, the necessary setup and infrastructure for microfluidics experiments and in the long run help reduce the hydrometallurgical steps in complex metal recycling. Hence, it contributes to advancing the fields of battery recycling, microfluidics, and simultaneous crystallization.

Doctor of Philosophy / Department of Chemistry / Christopher T. Culbertson / Analytical separations form the bulk of experiments in both research and industry. The choice of separation technique is governed by the characteristics of the analyte and purpose of separation. Miniaturization of chromatographic techniques enables the separation and purification of small volume samples that are often in limited supply. Capillary electrophoresis and immunoaffinity chromatography are examples of techniques that can be easily miniaturized with minimum loss in separation efficiency. These techniques were used in the experiments presented in this dissertation. Chapter 1 discusses the underlying principles of capillary electrophoresis and immunoaffinity chromatography. In the second chapter, the results from immunoaffinity chromatography experiments that utilized antibody-coated magnetic beads to purify serine proteases and serine protease inhibitors (serpins) from A. gambiae hemolymph are presented and discussed. Serine proteases and serpins play a key role in the insect innate immunity system. Serpins regulate the activity of serine proteases by forming irreversible complexes with the proteases. To identify the proteases that couple to these serpins, protein A magnetic beads were coated with SRPN2 antibody and then incubated with A. gambiae hemolymph. The antibody isolated both the free SRPN2 and the SRPN2-protease complex. The purified proteases were identified by ESI-MS from as few as 25 insects. In Chapter 3, an integrated glass/PDMS hybrid microfluidic device was utilized for the transportation and lysis of cells at a high throughput. Jurkat cells were labeled with 6-CFDA (an internal standard) and DAF-FM (a NO specific fluorophore). Laser-induced fluorescence (LIF) detection was utilized to detect nitric oxide (NO) from single Jurkat cells. The resulting electropherograms were used to study the variation in NO production following stimulation with lipopolysaccharide (LPS). 3 h LPS-stimulation resulted in a two fold increase in NO production in both bulk and single cell analysis. A comparison of bulk and single cell NO measurements were performed and the average NO production in single cells compared well to the increase measured at the bulk cell level. Chapter 4 discusses the preliminary experiments with a T-shaped microfluidic device that exploit the property of poly(dimethylsiloxane) (PDMS) as an electroactive polymer (EAP), to enhance fluid mixing. EAPs deform when placed in an electric field. A thin layer of PDMS was sandwiched between chrome electrodes, positioned on the horizontal arms of the T design, and the electrolyte-filled fluidic channel. A potential difference across the PDMS layer caused it to shrink and stretch, thereby increasing the channel volume. The electrodes were actuated at 180[degrees] out of phase and this caused the fluid stream in the vertical channel to fold and stretch resulting in enhanced contact surface area and shorter diffusion distances of the fluid, thereby improving mixing efficiency. All the experiments presented in this dissertation demonstrate the application of miniaturized chromatographic techniques for the efficient analysis of small volume biological samples.

Master of Science / Department of Chemistry / Christopher T. Culbertson / Circulating tumor cells (CTCs) have become a key component in the identification and treatment of cancer. Once dislodged from the main tumor, CTCs travel through the bloodstream and cause metastasis. Early detection and identification of these cells can help in the evaluation and prognosis of various types of cancer, as well as assisting in patient treatments by determining the spread of the disease. Here, a high-throughput microfluidic analysis technique is described that can efficiently detect and identify cells, with the specific identification of CTCs as a future application through fluorescent labeling in mind. As proof of principle, the device has been shown to detect and characterize individual human Jurkat (T-lymphocyte) cells at a rate of 100 cells/minute. The device employs micro-scale flow focusing to isolate individual cells. The cells are detected using both light scattering and laser-induced fluorescence to evaluate cell size and surface functionality.

Doctor of Philosophy / Department of Chemistry / Christopher T. Culbertson / As the field of separation science evolves so do the techniques, tools and capabilities of the discipline. The introduction of microfluidics stemmed from a desire to perform traditional analyses faster and on a much smaller scale. The small device sizes exploited in microfluidics permits the investigation of very small volumes of very dilute samples yielding information inaccessible by traditional macroscale techniques. All of the chapters presented in this dissertation illustrate attempts to supplement current microscale techniques with new tools, techniques and analysis schemes for looking at biologically relevant analyses. In chapter two I present the development and characterization of an amphiphilic polymer that has potential as a material for the fabrication of microfluidic devices. This material is composed of a poly(dimethylsiloxane)-poly(ethylene oxide) block copolymer and is dramatically more hydrophilic than the other polymeric materials currently used for the fabrication of microfluidic templates, mainly poly(dimethylsiloxane). Biomolecules such as proteins are notoriously hydrophobic and will tend to adsorb to other hydrophobic surfaces thus the use of a hydrophilic material may serve to reduce or eliminate this problem. The amphiphilic material is of a suitable durability for micromolding and molded channel architectures can be sealed between two layers of the material by simple conformal contact permitting the execution of high speed electrophoretic separations. Chapter three contains initial results obtained while investigating the fluorescent labeling and electrophoretic separation of ecdysteroids. Ecdysteroids are hormones found in insects that are responsible for controlling the process of molting. Here we attempted to analyze these molecules by employing a reactive fluorescent probe, BODIPY FL® hydrazide, that would target the α,β-unsaturated ketone group on the steroid, permitting its analysis by capillary electrophoresis with laser induced fluorescence detection. While optimistic initial results were obtained with the labeling and analysis of similar functional groups on model compounds such as progesterone, labeling of the ecdysteroid molecules was never achieved to a degree that would permit reliable analysis. In chapter four I report the development and use of a microimmunoaffinity column for the analysis of insect serine protease inhibitors, or serpins. These proteins play a very important role in the regulation of insect immune responses and their activity may play an integral role in the effective transmission of the malaria parasite by the mosquito Anopheles gambiae. A microimmunoaffinity column was constructed from magnets, poly(dimethylsiloxane), fused silica capillary and Protein A coated magnetic microspheres. In these initial studies, purified antibodies to serpin protein, as well as purified serpin protein, were used to prepare and investigate the ability to isolate, preconcentrate, and elute serpin proteins for subsequent analysis. By implementing this miniaturized system which incorporates very small fluid volumes we hoped to extend this technique to the analysis of very small samples, and eventually to the analysis of individual small insects. Our work indicates that it is possible to isolate, elute, and detect serpin protein on a traditional western blot membrane. Chapter five presents the development of a novel polymer blend for the fabrication of paper-based microfluidic devices and use of these devices in the performance of diagnostically relevant clinical assays. We took the concept of paper-based microfluidic devices and improved upon the current photoactive polymers used for their fabrication by developing a polymer blend using an acryloxy modified siloxane polymer as well as a commercially available photoactive adhesive, Norland Optical Adhesive 74. This blended polymer resulted in a dramatic reduction in fabrication time as well as improved resolution permitting the reliable patterning of small feature sizes. We also report for the first time a demonstration of these devices performing a two-step spatially separated online chemical derivatization facilitating the analysis of urinary ketones. These devices are predominantly used for the analysis of urine, and their application was extended to the quantitation of nitrite in saliva for the purposes of hemodialysis monitoring. While varied in application, all of the data presented in this dissertation exploits the power of miniaturization to improve current methods of analysis and to extend macroscale techniques to trace biological analytes.

Capillarity and dynamic wetting of non-Newtonian fluids are important in many natural and industrial processes, examples cover from a daily phenomenon as splashing of a cup of yogurt to advanced technologies such as additive manufacturing. The applicable non-Newtonian fluids are usually viscoelastic compounds of polymers and solvents. Previous experiments observed diverse interesting behaviors of a polymeric droplet on a wetted substrate or in a microfluidic device. However, our understanding of how viscoelasticity affects droplet dynamics remains very limited. This work intends to shed light on viscoelastic effect on two small scale processes, i.e., the motion of a wetting contact line and droplet splitting at a bifurcation tip.   Numerical simulation is employed to reveal detailed information such as elastic stresses and interfacial flow field. A numerical model is built, combining the phase field method, computational rheology techniques and computational fluid dynamics. The system is capable for calculation of realistic circumstances such as a droplet made of aqueous solution of polymers with moderate relaxation time, impacting a partially wetting surface in ambient air.   The work is divided into three flow cases. For the flow case of bifurcation tube, the evolution of the interface and droplet dynamics are compared between viscoelastic fluids and Newtonian fluids. The splitting or non-splitting behavior influenced by elastic stresses is analyzed. For the flow case of dynamic wetting, the flow field and rheological details such as effective viscosity and normal stress difference near a moving contact line are presented. The effects of shear-thinning and elasticity on droplet spreading and receding are analyzed, under inertial and inertialess circumstances. In the last part, droplet impact of both Newtonian and viscoelastic fluids are demonstrated. For Newtonian droplets, a phase diagram is drawn to visualize different impact regions for spreading, splashing and gas entrapment. For viscoelastic droplets, the viscoelastic effects on droplet deformation, spreading radius and contact line motion are revealed and discussed. / <p>QC 20160329</p>

Thesis (PhD (Process Engineering))--University of Stellenbosch, 2010. / ENGLISH ABSTRACT: The ongoing trend in papermaking industries is to lower production costs by increasing the low cost filler content in the sheets. However, the disruption of inter-fibre bonding is accompanied by a deterioration of paper stiffness and mechanical properties if filler content exceeds 18 wt%. Polysaccharide solutions, such as starch, are often used as a low cost biodegradable additive to improve internal sheet strength when added to the wet-end of production. The amount of starch that can be added is however limited as only a small percentage will be retained in the paper web. A dual additive multifunctional polysaccharide system was developed to allow higher filler loading levels without detrimental deterioration in paper properties. In order to achieve a larger surface area for fibre/filler interaction and to reduce drainage losses, at least one of these additives was in particulate form. Anionic, cationic, and unsaturated derivatives were prepared using sodium monochloroacetate, 3-chloro-2-hydroxypropyltrimethylammonium chloride, and allyl bromide, respectively. The degree of substitution was determined by 1H-NMR spectroscopy and back titration methods and the interaction of the ionic modified derivatives with paper components was determined using fluorescence microscopy. Anionic modified polysaccharide particles were prepared using techniques such as macrogel ultrasonification, water-in-water emulsification, and in-situ cross-linking and carboxymethylation of granular starch. A process of adding sequential layers of oppositely charged polyelectrolyte layers onto the filler particles was also investigated. A novel approach of preparing modified particles with tailored size and distribution using microfluidics was studied and modelled using response surface methodology. Hand sheets were prepared using the dual additive system and improvements in stiffness, tear resistance, breaking length, and folding endurance were observed. The modified granular maize starch particles had a pre-eminent effect on improving stiffness at higher filler loadings (14% improvement at 30 wt% filler loading), while bulky particles prepared using microfluidics showed a more consistent improvement (between 6% and 10%) across the loading range. Overall improvements gained by the introduction of multi-layered soluble polymers onto fillers suggest that the introduction of nanotechnology to the papermaking process should be of potential benefit to the industry. Furthermore, the dual additive system developed during the course of this study should also be tested on a continuous pilot plant papermaking process. / AFRIKAANSE OPSOMMING: Die papierindustrie neig voortdurend daarna om produksiekostes te verlaag deur die persentasie lae koste vulstof wat gebruik word te verhoog. Aangesien die vulstof vesel kontak belemmer, gaan hoër vlakke (> 18 wt%) egter gepaard met ’n verlaging in papier styfheid en meganiese eienskappe. Polisakkaried oplossings, soos byvoorbeeld stysel, word dikwels gebruik as lae koste vergaanbare bymiddel om papier intern te versterk wanneer dit voor die vormingsproses bygevoeg word. Slegs ’n beperkte hoeveelheid stysel word egter behou in die papier matriks en oormatige oplossings ontsnap tydens dreinering in die afvalwater. ’n Dubbele multi-funksionele polisakkaried bymiddelsisteem was ontwikkel wat ongewensde verwakking in papiereienskappe verminder tydens vulstof verhogings. Ten minste een van die bymiddels was in partikelvorm om sodoende ’n groter oppervlak te bied vir vesel/vulstof interaksie en om dreineringsverliese te verminder. Anioniese, kationiese, sowel as onversadigde derivate was berei deur onderskeidelik gebruik te maak van natrium monochloroasetaat, 3-chloro-2-hidroksiepropieltrimetielammonium chloried, en alliel bromied. Die graad van substitutiese was bepaal met behulp van 1H-KMR spektroskopie sowel as titrasie tegnieke terwyl die ioniese interaksie van die gemodifiseerde stysels met die papierkomponente ondersoek was met behulp van fluoressensie mikroskopie. Anioniese polisakkaried partikels was berei met tegnieke soos makro-jel ultrasonifikasie, water-in-water emulsifikasie, en in-situ kruisbinding en karboksiemetielasie van stysel granulate. ’n Proses was ook ondersoek waar vulstof partikels omhul was in verskeie lae poliëlektroliet oplossings. ’n Nuwe benadering was toegepas waar gemodifiseerde partikels met voorafbepaalde grootte en verspreiding berei is deur gebruik te maak van mikrofluïdika en gemodelleer met behulp van oppervlakte ontwerp metodeleer. Papier toetse was uitgevoer met die bymiddelsisteem en algehele verbetering in styfheid, skeurweerstand, breeklengte, en voulydsaamheid is waargeneem. Die gemodifiseerde stysel granulate het die grootste verbetering in styfheid by hoë vulstofladings getoon (14% verbetering by 30 wt% vulstoflading) terwyl die groter mikrofluïdika-bereide partikels algehele verbetering (tussen 6% en 10%) getoon het oor die hele vulstoflading reeks. Die verbeteringe in styfheid sowel as meganiese eienskappe van papier voorberei met poliëlektroliet omhulde vulstof toon dat aanwending van nanotegnologie in hierdie bedryf potensieel voordelig kan wees. Opskalering van die polisakkaried bymiddels ontwikkel gedurende hierdie studie behoort uitgevoer te word vir verdere toetse op ’n kontinue papier loodsaanleg.

The present thesis work deals with the development of a novel manufacturing protocol for the realization of excimer laser micro-patterned freestanding hydrogel layers (50 to 300 ??m thickness) based on thermo-responsive poly-(N-isopropyl)acrylamide (PNIPAAm) which can operate as temperature-triggered actuators for cells-on-chip applications. PNIPAAm based thin films were synthesized in house and manufactured by an injection/compression moulding based technique in order to obtain flat hydrogels attached to rigid polyvinyl chloride (PVC) substrates to facilitate laser focusing. Laser machining parameters were empirically optimized to fabricate arrays of through-holes with entrance diameter ranging from 30 ??m to 150 ??m and having different exit diameter (from 10 to 20 ??m) on the PNIPAAm employing a stencil aluminum mask. After laser processing, the microstructured layers were detached from the PVC using a chemical treatment and then left to swoll in pure water. The KrF excimer laser machined through-holes could be reversibly modulated in terms of size as a consequence of the polymer volumetric phase transition induced by a temperature change above the critical value of 32 ??C. Thermo-responsiveness characterization was carried out on the detached water swollen freestanding layers using a thermostat bath, by changing the temperature from 18 ??C to 39 ??C and each sample could undergo multiple cycles. As a result of the polymer water loss, the shrinkage of the layer caused the holes to shrink homogeneously, thus reducing their original size of about the 50% in the polymer collapsed state. To prove the functionality of these stimuli-responsive smart surfaces in the frame of cells-on-chip systems, they were integrated in a multilayer microfluidic device to operate as self-regulating cell sorting actuators for single cell assays applications. Using mechanical fastening as the packaging strategy, the hydrated hydrogel was sealed between two micro-milled poly-methyl methacrylate (PMMA) components, which provided the fluid accesses and ducts to the cell suspension to be flown over the thermoresponsive actuator (top layer) and the well to collect the sorted sample (bottom layer). The device is also equipped with a thin transparent heater to control the microfluidic chip temperature. When the system is assembled, the temperature-triggered actuation mechanism was exploited to trap a cellular sample in the shrunken exit hole on the top of the hydrogel layer by applying a negative pressure across the film via the bottom PMMA component when the system is kept at 37 ??C. Subsequently, the sorting of the trapped cell took place through the micro-capillary when the polymer natural relaxation at room temperature towards its initial state occurred; the operational principle of the device was proved using MG63 cells as a model cell line by monitoring the sorting through the size-modulating structures using optical microscopy.

No description available.

Over recent years the delivery of nanosized drug particles has shown potential in improving bioavailability. Drug nanosizing is achieved by 'top-down' and by 'bottom-up' approaches. Owing to limitations associated with the top-down techniques, such as high energy input, electrostatic effects, broad particle size distributions and contamination issues, great interest has been directed to alternative bottom up technologies. In this study, the hypothesis that microreactors can be used as a simple and cost-effective technique to generate organic nanosized products is tested using three steroids (hydrocortisone, prednisolone and budesonide). Arrested antisolvent nanoprecipitation using ethanol (solvent) and water (antisolvent) was conducted within the microreactors. To enable experimental design for the microreactor studies, solubility profiles in different ethanol-water combinations at 25 °C were explored. All three drugs' solubility increased with increasing ethanol concentration showing maxima at 80-90 % v/v ethanol-water mixtures. Because of the complex multivariate microfluidic process, artificial neural network modelling was then employed to identify the dominant relationships between the variables affecting nanoprecipitation (as inputs) and the drug particle size (as output). The antisolvent flow rate was found to have the major role in directing drug particle size. Based on these successful findings, the potential of preparing pharmaceutical nanosuspensions using microfluidic reactors was researched. A hydrocortisone (HC) nanosuspension (NS) was prepared by introducing the generated drug particles into an aqueous solution of stabilizers stirred at high speed with a propeller mixer. A tangential flow filtration system was then used to concentrate the prepared NS. Results showed that a stable narrow sized HC NS of amorphous spherical particles 500 ± 64 nm diameter and zeta potential -18 ± 2.84 mV could be produced. The ocular bioavailability of a microfluidic precipitated HC NS (300 nm) was assessed and compared to a similar sized, milled HC NS and HC solution as a control. The precipitated and the milled NS achieved comparable AUC0-9h of 28.06 ± 4.08 and 30.95 ± 2.2, respectively, significantly (P < 0.01) higher than HC solution (15.86 ± 2.7). These results illustrate the opportunity to design sustained release ophthalmic formulations. Going nano via microfluidic precipitation was also exploited to tailor budesonide (BD) NS for pulmonary administration. The in vitro aerosolization by nebulization of a BD NS was studied in comparison with a commercial BD microsuspension. Overall, the fine particle fraction generated from BD NS (56.88 ± 3.37) was significantly (P < 0.05) higher than the marketed BD (38.04 ± 7.81). The mean mass aerodynamic diameter of BD NS aerosol (3.9 ± 0.48 μm) was significantly smaller (P < 0.05) than the microsuspension (6.2 ± 1.09 μm) indicating improved performance for BD NS. In conclusion, findings of this study support the hypothesis of using microfluidic nanoprecipitation as a promising and economical technique of drug nanosizing.

This work focuses on the integration of microfluidics and dielectrophoresis(DEP) with the principles of field flow fractionation (FFF) to create a continuous-flow isolator for rare and viable circulating tumor cells (CTCs) from peripheral blood mononuclear cells (PBMNs) drawn from cancer patients. The method exploits differences in the plasma membrane capacitances of tumor and blood cells, which correspond to differences in the membrane surface areas of these cell types. DEP-FFF was first adapted to measure cell membrane capacitance, cell density and deformability profiles of cell populations. These properties of the NCI-60 panel of cancer cell types, which represents the wide functional diversity of cancers from 9 organs and leukemia, were compared with the normal cell subpopulations of peripheral blood. In every case, the NCI-60 cells exhibited membrane capacitance characteristics that were distinct from blood and, as a result, they could be isolated from blood by DEP. The heightened cancer cell membrane capacitances correlated strongly with membrane-rich morphological characteristics at their growth sites, including cell flattening, dendritic projections, and surface wrinkling. Following harvest from culture and maintenance in suspension, cancer cells were found to shed cytoplasm and membrane area over time and the suspended cell populations developed considerable morphological diversity. The shedding changed the cancer cell DEP properties but they could still be isolated from blood cells. A similar shedding process in the peripheral blood could account for the surprisingly wide morphological diversity seen among circulating cells isolated from clinical specimens. A continuous flow DEP-FFF method was devised to exploit these findings by allowing CTCs to be isolated from the nucleated cells of 10 mL clinical blood specimens in 40 minutes, an extremely high throughput rate for a microfluidic-based method. Cultured cancer cells could be isolated at 70-80% efficiency using this approach and the isolation of CTCs from clinical specimens was demonstrated. The results showed that the continuous DEP-FFF method delivers unmodified, viable CTCs for analysis, is perhaps universally applicable to isolation of CTCs from different cancer types and is independent of surface antigens - making it suitable for cells lacking the epithelial markers used in currently accepted CTC isolation methods. / text