ANALIZA VPLIVOV OBLIKE MAGNETOV NA SAMODRŽNI MOMENT MOTORJA S TRAJNIMI MAGNETIJure Strnad
, 2009, diplomsko delo
Opis: V diplomskem delu je obravnavan motor s trajnimi magneti, ki se zaradi številnih dobrih lastnosti vse pogosteje uporablja v novejših električnih pogonih. Delo prikazuje projektiranje motorja s trajnimi magneti, ter konstrukcijsko zniževanje samodržnega vrtilnega momenta, ki je pri tem tipu motorja vedno prisoten. Izračuni vrtilnega momenta ter analize magnetnih razmer na osnovi 3D modela motorja so narejene s pomočjo programskega paketa Vector Fields — Opera, kateri deluje na osnovi metode končnih elementov. Za primerjavo so narejene magnetne analize treh različnih oblik polov trajnih magnetov.
Ključne besede: Motor s trajnimi magneti, samodržni vrtilni moment, metoda
končnih elementov, numerična analiza.
Objavljeno: 01.10.2009; Ogledov: 2315; Prenosov: 208
Celotno besedilo (1,40 MB)
Optimization of cultivation conditions for mammalian cell lines producing complex biosimilarsJure Strnad
, 2011, doktorska disertacija
Opis: EXTENDED ABSTRACT
The possibility to replace standard single use 250 mL shake flasks with single use 50 mL spin tubes was investigated using the design of experiments methodology. Experimental throughput could be tripled to a maximum of 120 spin tubes per shaker-incubator unit if similar process performance could be proven in shake flasks and spin tubes. A D-optimal response surface design was used to model titer values in a seven day batch process producing recombinant erythropoietin. Shaking rate and working volume in spin tubes were adjusted to simulate titers that are produced in shake flasks at the reference setting. Research results indicated that equivalent titers as in shake flasks at the reference setting can be produced in spin tubes; moreover, even higher titers are possible. The maximal titers in spin tubes reached values as observed in 6 L bioreactors. Furthermore, a comparison of process performance and product quality attributes between two spin tube settings, the reference shake flask setting, a standard bioreactor run and a bioreactor run without pH control was made. Process performance and product quality attributes in spin tubes at the equality setting (shaking rate of 180 rpm and 30 mL working volume) were comparable to the ones derived from the reference shake flask setting. Results derived for both bioreactor runs were not fully comparable to the spin tube and shake flask systems. The statistical model for calculating titers on day seven of a batch process in spin tubes was successfully validated and can be used for titer prediction in the proposed design space.
The optimized spin tube settings were further used in a repetitive batch process where in the harvest phase of the process medium was daily exchanged to prevent component depletion or build-up of inhibitors. Spin tubes and shake flasks were used to simulate the industrial process of erythropoietin production. The effect of process mode change from seven-day batch to repetitive batch was investigated on process performance and product quality attributes, such as isoform distribution and glycan group distribution. Spin tube performance at the equality setting was comparable to the shake flask performance also in the repetitive batch process. Performance, especially titers at the maximal titer spin tube setting was, however, not fully comparable to the results obtained in previous optimization experiments.
The spin tube equality setting was also used for cultivating two cell lines producing different monoclonal antibodies. The goal was to investigate how different cell lines influence process performance and product quality attributes, such as monoclonal antibody charge variant distribution and glycan group distribution. Both cell lines were derived from a Chinese hamster ovary parental cell line, therefore, it was proposed that maybe the optimal spin tube setting derived for the erythropoietin producing cell line, which was also derived from the Chinese hamster ovary parental cell line, could also be used for these subtypes. Cell growth of the monoclonal antibody producing cell lines was extensively better as observed for the erythropoietin producing cell line, which meant that culture demands were more pronounced, such as oxygen transfer or mass transfer. It was observed that the erythropoietin derived equality spin tube setting did not produce similar process responses as shake flask at the reference setting for both monoclonal antibodies. The foremost difference was that the metabolite lactate was being consumed in shake flasks after it reached a maximum value but was not consumed in spin tubes for both monoclonal antibody producing cell lines. In these experiments also amino acid time profiles during a seven day batch process were monitored and subsequently compared. It was seen that several amino acids seemed to be in excess as most of them were only half way consumed. Product quality attributes also differed between the spin tube and the shake flask setting. The conclusion of the experimental work was that some fine tuning of th
Ključne besede: design of experiments, spin tube, shake flask, optimization, erythropoietin, monoclonal antibodies
Objavljeno: 22.12.2011; Ogledov: 2419; Prenosov: 124
Celotno besedilo (6,72 MB)
Optimal process mode selection for clone screeningJure Strnad
, Vatroslav Spudić
, Matjaž Brinc
, Jerica Rozman Pungerčar
, Zdravko Kravanja
, 2011, izvirni znanstveni članek
Opis: A significant amount of data is generated during clone screening procedures because several cultivation systems are used such as well-plates, shake-flasks, laboratory-scale bioreactors among others. The amount of data can often be staggering and thus requires the use of statistical and data mining procedures in order to extract hidden information. In regard to a biosimilar monoclonal antibody project, data from the shake-flask scale was observed when comparing batch and fed-batch processes for several individual clones derived from two different cell lines. The aim of the research presented in this paper was to determine if clone selection based on batch data during the initial screening phase was equivalent to the results from fed-batch selection. It was determined that fed-batch processes should be implemented early during the screening procedure, if a choice is made that the final manufacturing process should also be operated in a fedbatch mode, as clone selection based on both batch and fed-batch analytical data was divergent.
Ključne besede: monoclonal antibody, batch, fed-batch, clone screening, glycosylation, charge variants
Objavljeno: 01.06.2012; Ogledov: 1196; Prenosov: 37
Celotno besedilo (654,73 KB)
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