The enhanced axial mixing which is caused by dispersion in oscillatory flows in some mass transfer devices may limit the reactor performance. This effect has provided the motivation for the present study in which oscillatory flow dispersion in a flat channel of large aspect ratio is investigated. The rate of spreading of a uniform slug of some passive tracer has been predicted using numerical and analytical techniques and the results have been verified experimentally. The numerical approach has used a finite difference time-marching method to obtain predictions for the channel concentrations. From the results, the dispersion coefficient (D) has been evaluated for Strouhal numbers of O.O1→0.2 and for mean Reynolds numbers of O.4→2OO at Schmidt numbers (Sc) O(1O³) . It has been concluded that under these conditions D varies as stroke squared. Unless the flow is not quasi-steady (i.e. if pulsatile Reynolds number α²<O(l)) D is only a weak function of frequency. These predictions for the dispersion coefficient have been in excellent agreement with those of Watson (256). It has also been concluded from the numerical study that the phase of the velocity sinusoid at the instant of injection has a critical effect upon the form of the concentration evolution. An approximate analytical technique has been developed in which weighted mean cross-channel concentrations are defined. The wall concentration is expressed approximately using a Fourier series. This procedure leads to ordinary differential equations for the axial moments. When the axial variance of mean concentration and the dispersion coefficient were computed in this way for quasi-steady flows good agreement was obtained with the numerical work. Simple opto-electronic gauges have been developed to measure mean cross-channel concentrations. The sensors have been used to obtain experimental data for the dispersion coefficient of a furrowed channel mass transfer device using slug stimulus techniques. Experimental investigations of dispersion in oscillatory flows in a flat channel using these gauges has produced values for D which are in agreement with the theoretical predictions for quasi-steady flows.

Thesis (M.S.)--Oregon State University, 2007. / Printout. Includes bibliographical references (leaves 72-74). Also available on the World Wide Web.

More than 1.2 million people worldwide require regular hemodialysis therapy to treat end stage renal failure. In the United States alone, there are 300,000 patients and the National Kidney Foundation predicts that this number will double in the next 10 years. Currently most dialysis patients receive treatment at a dialysis center and need three 4-5 hour treatments each week. While these treatments are useful, more frequent and longer duration dialysis better simulates natural kidney function. Consequently, at-home hemodialysis is expected to provide patients a better quality of life. Current hemodialysis systems are too expensive to support at-home hemodialysis. Cost drivers include the capital costs of the hemodialysis equipment and the raw material costs of expensive hemodialysis membranes. Microchannel hemodialysers have smaller form factors requiring significantly less membrane while enabling reductions in the size and cost of capital equipment. Microchannel devices are typically made by microchannel lamination methods involving the patterning, registration and bonding of thin laminae. Findings in this paper show that membrane utilization is highly dependent on registration accuracy with membrane utilization often dropping below 25%. Efforts here focus on the development of a self-registration method for assembling microchannel hemodialysers capable of supporting registration accuracies below 25 ��m over a 50 mm polycarbonate lamina. Using these methods, registration accuracies below 13 ��m were measured over a 50 mm scale. A mass transfer test article was produced with measured average one dimensional misregistration below 19 ��m with a demonstrated membrane utilization of 44.9% when considering both microchannel and header regions. Mass transfer results suggest that the device performed with a mass transfer area of 90.59 mm��. A design is proposed describing membrane utilization of over 79%. / Graduation date: 2013 / Access restricted to the OSU Community at author's request from 9-17-2012 - 9-17-2013

Thesis (M.S.)--Oregon State University, 2010. / Printout. Includes bibliographical references (leaves 112-114). Also available on the World Wide Web.

The marked increase in surface-to-volume ratio associated with microscale devices for hemodialysis leads to problems with hemocompatibility and blood flow distribution that are more challenging to manage than those encountered at the conventional scale. In this work, stable surface modifications with pendant polyethylene oxide (PEO) chains were produced on polycarbonate microchannel and polyacrylonitrile membrane materials used in construction of microchannel hemodialyzer test articles. These coatings were evaluated in relation to protein repulsion, impact on urea permeability through the membrane, and impact on bubble retention through single-channel test articles. PEO layers were prepared by radiolytic grafting of PEO-PBD-PEO (PBD = polybutadiene) triblock copolymers to microchannel and membrane materials. Protein adsorption was detected by measurement of surface-bound enzyme activity following contact of uncoated and PEO-coated surfaces with ��-galactosidase. Protein adsorption was decreased on PEO-coated polycarbonate and polydimethyl siloxane (PDMS) materials by 80% when compared to the level recorded on uncoated materials. Protein adsorption on membrane materials was not decreased with PEO-PBD-PEO treatment; a PEI (polyethylene imide) layer exists on the AN69 ST membrane which is intended to trap heparin during membrane pre-treatment. It is still unclear how this PEI layer interacts with PEO-PBD-PEO. Neither the PEO-PBD-PEO triblocks nor the irradiation process was observed to have any effect on polyacrylonitrile membrane permeability to urea, nor did the presence of additional fibrinogen and bovine serum albumin (BSA) in the urea filtrate. The PEO-PBD-PEO treatment was not able to visibly reduce bubble retention during flow through single-channel polycarbonate test articles, however, the rough surfaces of the laser-etched polycarbonate microchannels may be causing this bubble retention. This surface treatment holds promise as a means for imparting safe, efficacious coatings to blood processing equipment that ensure good hemocompatibility and blood flow distribution, with no adverse effects on mass transfer. / Graduation date: 2013

Les anticorps monoclonaux (AcM) sont des protéines ayant une reconnaissance antigénique spécifique utilisée pour le développement de réactifs thérapeutiques et diagnostiques. La production commerciale est réalisée en cultivant des cellules hôtes dans des bioréacteurs spécifiques. La densité cellulaire et le métabolisme cellulaire sont des paramètres clés pour le rendement élevé des AcM. Bioréacteur à fibres creuses (HFB), une cartouche contenant des fibres poreuses emballées, est l'un des systèmes de production disponibles dans le commerce. Si la densité de cellules obtenue peut conduire à un rendement élevé, le coût de l'ensemble du dispositif, y compris les pompes et les cartouches très coûteuses, empêche son utilisation de petites unités. Comme une alternative économique, nous avons proposé ici d'étudier le potentiel des modules de dialyse de polysulfone du commerce, classiquement employés dans le traitement de l'insuffisance rénale en phase terminale. Cependant, la membrane de polysulfone native a démontré une adsorption de protéines non spécifique significative préjudiciable à la production d'AcMs. De plus des enjeux normatifs viennent se greffer à ces problématiques scientifiques et technico-économiques, avec le cas des normes (ISO 13485/ AC S99-104/ GMP FDA /BPF…) qui imposent des méthodes de travail normalisées. Ce travail de thèse consiste en la conception d’un bioréacteur jetable, sur la base d’une cartouche de dialyse médicale à fibres creuses. Ce système doit offrir toutes les garanties en termes de production, de facilité d’utilisation, de stérilité, et permettre de concentrer les produits de cytoculture. La méthodologie scientifique a été couplée à une démarche qualité. La gestion de ce projet a été couplé à l’analyse de risques. En effet ce projet a été divisé en ses 5 composantes élémentaires décrite par Ishikawa par la méthode des 5 M. L’analyse de risque a consisté au calcul d’indice de criticité par la méthode AMDEC de chacune de ses familles de risques. Cette approche nous a permis de formaliser deux axes de recherche : i) la mise en œuvre d’une oxygénation efficace du milieu de culture (chapitre 4) et ii) les moyens de limiter le colmatage dans le module à fibres creuses pour obtenir une culture cellulaire conforme aux objectifs (chapitre 5). Le taux d’oxygénation est un facteur à prendre en compte dans un processus de culture cellulaire. L’oxygène peut être supplémenté selon deux modes, le mode passif ou le mode actif [Ozturk et Palsson 1990; Zhang S. et al 1992]. Il existe 2 types de système d’oxygénation : les système dit passif ou les échanges se font a travers une paroi de silicone et un système actif par aération directe dans le milieu de culture. Ce système est de loin l'opération la plus simple pour fournir de l'oxygène. Cependant, lorsque celui-ci est utilisé pour apporter de l’oxygène à des cultures de cellules mammifères, cela peut engendrer des altérations cellulaires. Des agents protecteurs chimiques peuvent être utilisés pour réduire les dommages cellulaires et la formation de mousse [Kamase et Moo-yung 1990; van Der pol L.A et al 1993]. Nos études ont démontré que l'addition d'agents anti-mousse peut entraîner une diminution du coefficient de transfert de masse d’O2 en phase liquide (Kl) [Kamase et Moo-yung 1990]. Nous avons établi l’efficacité de l’utilisation d’un polymère silice/silicone pour éliminer la mousse sur des cultures bactériennes et de cellules mammifères. Afin de limiter ces phénomènes de colmatage, les fibres de polysulfone ont été traitées avec plusieurs tensioactifs (acide pluronique F127, D-limonen et différentes huiles de silicone) qui ont conduit à une diminution significative de l'adsorption protéique. L'effet de ces surfactants sur les performances de filtration et sur la cytotoxicité a été étudié. Certains d'entre eux n'ont pas influencé ces paramètres alors que d'autres ont présenté des effets négatifs. / Monoclonal Antibodies (mAbs) are proteins with specific antigen recognition used for development of both therapeutic and diagnostic reagents. Commercial production is achieved by growing host cells in specific bioreactors. Cell density and cell metabolism are key parameters for high yield of mAbs. Hollow fiber bioreactor (I-IFB), a cartridge containing packed porous fibres, is one of the system for production commercially available. If the cell density achieved can lead to high yield, the cost of the whole device, including pumps and very expensive cartridges prevents its use of small units. As an economical alternative, we proposed here to investigate the potential of commercial polysulfone dialysis modules, classically employed in the treatment of end stage renal failure. However, the native polysulfone membrane demonstrated a significant non-specific protein adsorption detrimental to mAbs production. Moreover normative issues are added to these scientific and techno-economic issues, with the case of standards (ISO 13485 / AC S99-104 / GMP FDA / BPF ...) which impose standard working methods. This thesis consists of the design of a disposable bioreactor, based on a hollow-fiber medical dialysis cartridge. This system must offer all the guarantees in terms of production, ease of use, sterility, and allow to concentrate the cytoculture products. Scientific methodology has been coupled with a quality approach. The management of this project was coupled with the risk analysis. Indeed this project was divided into its 5 elementary components describe by Ishikawa by the 5M method. The risk analysis consisted in the calculation of the criticality index by the AMDEC method of each of its families of risks. This approach allowed us to formalize two research axes: i) the implementation of an effective oxygenation of the culture medium (chapter 4) and ii) the means of limiting the clogging in the hollow fiber module to obtain a culture consistent with the objectives (Chapter 5). The rate of oxygenation is a factor to be taken into account in a cell culture process. Oxygen can be supplemented in two modes, passive mode or active mode [Ozturk and Palsson 1990; Zhang S. et al 19921. There are two types of oxygenation system: the so-called passive system or the exchanges are made through a silicone wall and an active system by direct aeration in the culture medium. This system is by far the simplest operation for providing oxygen. However, when it is used to supply oxygen to mammalian cell cultures, this can cause cellular damage. Chemical protective agents can be used to reduce cell damage and DKamase and Moo-yung 1990 foam formation; van Der pol L.A. et al 1993 Cl. Our studies have shown that the addition of antifoaming agents can lead to a decrease in the liquid phase (K2) mass transfer coefficient of D Kamase and Moo-yung 1990C]. We have established the effectiveness of using a silica / silicone polymer to remove foam on bacterial and mammalian cell cultures. In order to limit these adsorption phenomena, polysulfone fibers were treated with several surfactants (pluronic acid F 127, D-limonen, and different silicone oils) which led to a significant decrease in protein adsorption. The effect of such surfactants on the filtration performances and on cytotoxicity were investigated. Some of the them did not influence these parameters while some presented negative effects. Finally, different cell culture parameters (cells densities, production yield, flow properties, fouling) were studied, as well as the performance of the bioreactor in perfusion continuous mode. The bioreactor was maintained in continuous mode for fifteen days and the production yield per batch was 250 mg of AcMs. The results obtained in this work allowed us to define the next steps to be taken, and are the subject of the Perspectives section.