Appraisal of the mixing performance of Single-Use shaken bioreactors

The pharmaceutical industry is at the forefront of the production of antibodies using mammalian cell-based cultures, with single-use technologies gaining prominence in the manufacturing process. At laboratory scale mammalian cells are usually grown in low shear devices, with disposable shaken bioreactors being largely employed in the early stages of bioprocess development. It has been a recent industry trend to use shaken bioreactors at large scale in the upstream process, performing cell culture in single-use bags which eliminate the need for cleaning in place, offer flexibility and lower production down-times. Single-use Orbitally Shaken Bioreactors (OSRs) consist of a shaker, a structural support to which a disposable bag conforms to and all ancillary connections and controllers. Production scale OSRs with single-use bags, employ the agitation principle of shaken flasks and microwell plates, providing a homogeneously single-use upstream scale-up process thus facilitating scaling-up and simplifying regulatory approval. The aim of the work is to characterize the mixing and flow dynamics in a cylindrical orbitally shaken bioreactor with conical bottoms of different heights. The rationale for a conical bottom is to ease the suspension of cells or microcarriers, which are used for the cultivation of cells not yet adapted for suspend culture, such as legacy cell lines and stem cells. The geometry of the conical bottom was designed so to be compatible with single-use bags, as the conical bottom is truncated and the cone obtuse. This study builds upon previous works of the research group (Weheliye et al 2013, Rodriguez et al. 2013, Rodriguez et .al. 2014, Ducci and Weheliye, 2014) for flat bottom reactors, where increases in Froude number were found to determine a mean flow transition and to increase the turbulence levels. The major objective of the current work is to determine the performances of shaken bioreactors with conical bottom, and to assess to what extent the mean flow and flow regime transitions already identified for a flat bottom are affected by the geometry variation. Particle Image Velocimetry, PIV, and Dual Indicator System for Mixing Time, DISMT, were employed to assess the mixing performances in the bioreactor with a conical bottom. DISMT (see Rodriguez et al., 2014) consists in a colorimetric method where two pH indicators are used to visualise the level of mixing reached after insertion of an acid solution. The findings of the current study provides insight into the flow of a single-use shaken bioreactor and offers a novel approach to design the next generation of products and improve scaling methodologies

Automation of a cell culture process with lager vessels

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Разработка игрового приложения с искусственным интеллектом в рамках языковой модели

Объект исследования: алгоритмы построения ассоциаций внутри языковой модели и их практическое применение. Цель работы: разработка игрового приложения "Кодовые имена" с возможностью замены реальных игроков искусственным интеллектом. Область применения: распространение с помощью сервиса Google Play Market. Результаты работы: эффективный алгоритм создания базы ассоциаций, алгоритмы искусственного интеллекта для игры "Кодовые имена", мобильное игровое приложение.Object of research: algorithms for constructing associations within a language model and their practical application. The purpose of the work: the development of the game application "Codenames" with the possibility of replacing real players with artificial intelligence. Scope: distribution using Google Play Market. The results of work: an effective algorithm for creation of association database, algorithms for artificial intelligence for the game "Codenames", a mobile game application

Orbital shaken bioreactor for influenza A virus production in high cell density cultivations

The majority of large scale cell culture processes is performed in stirred tank bioreactors (STR) and process development employs scale down models of the same bioreactor type. However, for screening of clones or process conditions at even smaller scale, shake flasks (SF) represent the most widely used model. Occasionally, SF allow for robust processes that cannot be transferred to STR because sensitive cells cannot cope with mechanical stress in STR due to stirring and aeration. Orbital shaken bioreactors (OSB) are a valuable alternative to STR as the transfer from SF to OSB is simplified because the systems rely on the same basic principles for mixing and aeration (e.g., bubble-free surface gassing). In particular, high oxygen transfer rates and short mixing times combined with low shear stress can also be achieved in OSB. These benefits may be even more pronounced in high density culture processes. Please click Additional Files below to see the full abstract

Оптимизация комплекса интернет-продвижения галереи «Орнамент»

Предмет ВКР – технологии Интернет-продвижения галереи "Орнамент". Цель данной дипломной работы – оптимизация технологий Интернет-продвижения галереи "Орнамент" для повышения известности компании. Методы: были использованы теоретический анализ литературы, мониторинг и анализ Интернет-ресурсов, общенаучные методы анализа, сравнения и дедукции, SWOT-анализ. Новизна и практическая значимость дипломной работы: заключается в том, что результаты исследования могут быть использованы для оптимизации Интернет-продвижения не только галереей "Орнамент", но и другими компаниями на рынке.Subject of research - Technology of Internet promotion of the gallery "Ornament". Aim of research - Optimization of technologies for Internet promotion of the Ornament gallery to enhance the company's reputation. Research methods: Theoretical analysis of literature, monitoring and analysis of Internet resources, general scientific methods of analysis, comparison and deduction, SWOT-analysis. Practical relevance: The results of the research can be used to optimize the Internet promotion not only by Ornament Gallery, but also by other companies on the market

Scale-down of an orbital shaken bioreactor: High cell density cultivation in perfusion mode and virus production

Application of single-use bioreactors has been commonly shown for several cell culture-based production systems including commercial vaccine production. Compared to stainless steel bioreactors, competitive cell growth characteristics as well as virus yields can be reached [1]. In addition to conventional stirred tank reactors (STR), wave bioreactors or orbital shaken bioreactors (OSBs) are available that rely on alternative mixing regimes. For small-scale screening of clones and media, cell maintenance and process optimization, OSBs are the most widely used system. Besides their simple design and ease of handling, OSBs allow for robust processes due to reduced mechanical stress caused by stirring and aeration [2]. Furthermore, scale-up (£ 2500 L) is simplified as larger OSBs rely on the same basic principles for mixing and aeration (e.g. bubble-free surface gassing). Particularly for high cell density (HCD) processes, high oxygen transfer rates, short mixing times, and low shear stress are beneficial. Until now, the step from spin tubes or shake flasks into larger OSBs was rather large, as only the OSB SB10-X (Kühner AG, Switzerland) with a minimum working volume (wv) of 4-5 L was available. In this study, a novel scale-down 3 L vessel module (wv = 1-3 L) for the OSB SB10-X was evaluated for cultivation of suspension BHK-21 cells (CEVA, Germany) in perfusion mode to HCD. Cultivation was carried out in serum-free medium in a 3 L and 10 L single-use standard bag with 3 L and 5 L initial wv and 100 and 70 rpm shaking frequency with a shaking diameter of 50 mm, respectively. For perfusion, an alternating tangential flow system (ATF2, Repligen) with a cut-off of 0.4 µm (SB10-X) and 0.5 µm (SB3-X), respectively, was used. Following an initial batch phase of 2-3 days, perfusion was initiated. After a complete media exchange, cells in the 3 L vessel module were infected with a fusogenic oncolytic virus (rVSV-NDV, recombinant vesicular stomatitis virus-Newcastle disease virus) at a cell concentration of 44.5x106 cells/mL at a multiplicity of infection (MOI) of 10-4. The obtained data were compared to a cultivation of BHK-21 cells in the standard SB10-X module (infection at a cell concentration of 12.5x106 cells/mL with yellow fever virus WHO 17D-213/77 with an MOI of 10-3) and to a cultivation in a 1 L STR. The novel 3 L vessel module allowed for a successful and direct scale-down utilizing the SB10-X backbone without the need for further optimization. For both the SB10-X and the 3 L vessel module, the ATF system was successfully coupled and cell concentrations of 32.7x106 cells/mL and 45.9x106 cells/mL were reached with high viabilities above 98%, respectively. A faster doubling time (tD=22 h) was observed in the 3 L vessel module compared to the SB10-X system (tD=27 h). For rVSV-NDV production, similar infectious virus titers were reached compared to perfusion cultivations of BHK-21 cells in a 1 L STR. Volumetric media consumption was significantly reduced in the 3 L vessel module, facilitating the implementation of OSB systems in non-industrial research environments. All in all, we demonstrated the adaptability and scalability of the single-use OSB system for the production of various viruses in HCD perfusion mode. References [1] Gallo-Ramirez, L. E., A. Nikolay, Y. Genzel, and U. Reichl. 2015. Bioreactor concepts for cell culture-based viral vaccine production. Expert Rev Vaccines 14 (9):1181-95. doi: 10.1586/14760584.2015.1067144 [2] Klöckner W, Diederichs S, Büchs J. Orbitally shaken single-use bioreactors. Adv Biochem Eng Biotechnol. 2014;138:45-60. doi: 10.1007/10_2013_188. PMID: 23604207

Разработка рекомендательной системы по подбору музыки

Разработка рекомендательной системы музыкиMusic recommendation system implementatio

Создание функциональной керамики на основе оксинитридов алюминия и кремния

Объектом исследования является керамика на основе оксида алюминия, оксида кремния, диоксида циркония, нитрида бора, нитрида кремния. Целью работы является исследование структуры и физико-механических свойств керамики на основе оксида алюминия, диоксида кремния, диоксида циркония, нитрида бора, нитрида кремния, полученной прессованием и спеканием наноструктурных порошков. В процессе исследования изучали технологические свойства оксидных порошков, проводили их механическую активацию, пластификацию, формовали и спекали керамические прессовки, изготавливали микрошлифы спеченных образцов для наноиндентирования и изучения микроструктуры. Были определены плотность прессовок и спечённых образцов, измерены модуль упругости и нанотвердость с использованием методики наноиндентрования.The object of the study is ceramics based on aluminum oxide, silicon dioxide, zirconium dioxide, boron nitride, silicon nitride. The aim of this work is to study the structure and physical and mechanical properties of ceramics based on aluminum oxide, silicon dioxide, zirconium dioxide, boron nitride, silicon nitride obtained by pressing and sintering nanostructured powders. In the process of research, the technological properties of oxide powders were studied, their mechanical activation, plasticization, molding and sintering of ceramic compacts, microsections of sintered samples for nanoindentation and microstructure studying. The density of compacts and sintered samples was determined, the modulus of elasticity and nanohardness were measured using the nanoindentation technique