Sartorius the univessel su is suitable for mammalian, insect and plant cell culture in scales up to two liters volume. The world leader in serving science improving single use bioreactor design and process development. Characterisation and scaleup considerations of singleuse. An overview of bioreactors types, their design and properties will be considered for biomolecules production such as biomass, enzymes, organic acids, aroma compounds, spores, mushroom production. In cell culturebased vaccine production, scaleup of adherent cells is challenging. Pdf process parameters study of amylase production in a packed. Scaling up and design of bioreactors scale up deals with transferring laboratory or pilot plant data to commercial production. B when citing this work, cite the original article.
Nonstirred, aerated vessels are used in the process for traditional products such as wine, beer and cheese production. Scaleup of cell culture bioreactors using biomechatronic design. Bioreactor, cell culture, large scale, mass transfer, mixing, scale up, stirred tank full text the full text of this article is available as a pdf 3. This is the authors version of the published article. Testing and simulation approaches for singleuse bioreactor. Different agitation strategies are used to scaleup a process including speci. Singleuse technology and support for solving your biomanufacturing challenges the ideal bioreactor production operation the objectives of bioreactor production are to maximize productivity and efficiency while maintaining product quality. Oct 27, 2017 design, characterization, and scaleup strategy for a new singleuse productionscale bioreactor gennews. The only practical way to scaleup volumes of mesenchymal stem cells mscs is by using microcarriers in singleuse bioreactors, say scientists from astar and instituto superior tecnico. We have invested a major effort to make our bioreactors more efficient and to provide them with the best parameters. In silico prediction of largescale microbial production performance. The bioreactors fermenters of the i series are highly automated fermentation systems, available from 250 liters up to 30 m 3, 8. In this article, a new approach for cell culture bioreactor scaleup is suggested that is b ased on biomechatronic design methodology. Two dozens of new ideas and innovations allow high quality of measurement and control of six parameters essential for a good reproducibility of runs.
Using an embedded transmitter from mettlertoledo, an industry standard, for monitoring ph and do with standard. Stirred tank bioreactors are generally constructed to standard dimensions. Scaling up bioreactors fluid dynamics by applying analytical techniques often reserved for largescale industrial bioreactors to smaller labbased counterparts, researchers. This theoretical product has recently undergone upscaling to 200 l bioreactors from 5 l bioreactors in the context of moving from a successful phase ii to phase iii. In this context, the aim of this study was to evalu. The air that is used to lift up is sufficient to stir up the contents. Scaleup of aerobic fermentations is often carried out on the basis of a constant oxygen transfer coefficient. What will i learn why a square crosssection brings significant advantages to the upstream process, for handling, process assurance, while maintaining optimal cell culture performance. Fermentation was carried out in a glasscolumn reactor 15 cm in length.
The bottomup concept can be applied to merge already existing. Scalingup stem cells with singleuse bioreactors and. Process scale up between 3 different stirred tank bioreactors was studied. Jul 14, 2014 bioreactors come in reusable or singleuse formats, with the latter increasingly available. First, the most used measuring methods are revised. Cooling can be provided by either making the draught. Scaleup of cell culture bioreactors is a challenging engineering work that requires wide competence in cell biology, mechanical engineering and bioprocess design. Outline terminology bioprocess, bioprocessing, biochemistry, biotechnology. Despite success with automated model setup and identification, manual curation of the. Scaling up your cell cultures to bioreactors biocompare. The development of genetic engineering have played a major role in. Scaleup of cell culture bioreactors using biomechatronic.
Perfusion solutions can offer very costefficient scale up solutions, driving down operating costs due to the smaller equipment and facilities. The worlds most innovative bioreactor for your lab based on over thirty years of personal experience in the field, we have tried to analyze what is necessary for efficient, modern bioreactors and select the best technical solutions, which would lead to best performance. This chapter comprises engineering aspects of bioreactor systems design, operation, scale up developed or adapted for cultivation of mammalian cells, such as bioreactors for suspension culture stirredtank reactors, bubble columns, and airlift reactors, fixed bed and fluidized bed reactors, hollow fiber and membrane reactors, and, finally. Scaleup and scaledown methodologies for bioreactors. The high loading of lignocellulosic substrates could merge the. Typically, this refers to a bioreactor in which the lining in contact with the cell culture will be plastic, and this lining is encased within a more permanent structure typically, either a rocker or a cuboid or cylindrical steel support. Observations on scaleup yusuf chisti department of chemical engineering, university of waterloo, waterloo, ontario, canada n2l 3gl received 26 october 1992. But over the course of development, biopharmaceutical companies need more material for characterization, trial runs, and finally for commercialization. Design, characterization, and scaleup strategy for a new singleuse productionscale bioreactor gennews. As another example, a multipronged approach can also be used to i demonstrate equivalent performance between traditional alloy and proposed singleuse equipment, ii validate cfd simulation, and iii extend performance projections to intermediate and full scale equipment. Use bioreactors by emily stoker, master of science utah state university, 2011 major professor. Manual for monitoring unsaturated regions of the vadose zone at rcra. This chapter comprises engineering aspects of bioreactor systems design, operation, scaleup developed or adapted for cultivation of mammalian cells, such as bioreactors for suspension culture stirredtank reactors, bubble columns, and airlift reactors, fixed bed and fluidized bed reactors, hollow fiber and membrane reactors, and, finally, disposable bioreactors. Singleuse bioreactors have reached the big time biopharm.
It replicates the characteristics of classical bioreactors at microscale 10 to 15ml, by using costeffective, disposable micro bioreactor vessels, controlled by an automated. Bioreactor with a new innovative concept for all types of cell cultures on laboratory scale from 35 ml to 6 l culture volumes. Anaerobic bioreactors in aerobic bioreactors, the effect of agitation is obvious due to the effect on bubble size and holdup. A read is counted each time someone views a publication summary such as the title, abstract, and list of authors, clicks on a figure, or views or downloads the fulltext.
The term fermentor is used as synonym to bioreactors. For example, sartorius offers systems for singleuse bioreactors, such as the smaller ambr systems or the larger biostat system, that facilitate scaling up from conventional cell cultures. Poor mixing can lead to ph and nutrient gradient in largescale bioreactors bylund et al. Bioreactor scaleup and oxygen transfer rate in microbial. Pavel k scaleup and down modeling of bioreactors is a valuable tool to support process characterization and improvement in a predictable, timely, and costeffective manner. In silico prediction of largescale microbial production.
Typical applications range from small scale protein expression to media or process optimization studies. New research towards intensifying seedtrain and scaleup methods using 5. Ledoux 73 that plant cells could take up and integrate dna remained controversial. Development of an industrial biotechnology process using. While it is desirable to keep as many operating parameters constant as possible during the scale up, the number of constant parameters realizable is limited by the degrees of freedom in designing the large scale operation. Finally, to my fiance, who would always help me troubleshoot and could always see. Design, characterization, and scaleup strategy for a new. Air lift bioreactors the stirred tank bioreactors lack well defined flow of air. However, we did not adjust the sparge strategy during this experiment when do exceeded 30 % because cho cell cultures are typically insensitive to do at levels between 10 and 80 % of air saturation restelli et al. Effective scale up is essential for successful bioprocessing. The emergence of a variety of geometrically dissimilar singleuse bioreactor platforms provides users with both challenges and opportunities as they look to incorporate this technology across the range. Some scientists and engineers in biotech industry dedicate their entire careers scaling up various bioreactor processes, and each time they may encounter something new. Mscs are multipotent stromal cells that can differentiate into a variety of cell types which are being investigated for tissue engineering and cellular.
The degassed liquid then flows down the annular space outside the draft to the bottom of the bioreactor. Microcarrier mcbased suspension culture processes have been used to culture anchoragedependent cells in bioreactors. Bioreactors are basically mixing vessels with a simple function. In recent years, several automated scaledown bioreactor systems have been developed to increase efficiency in cell culture process development. However, scaleup of the process for high cell growth and productivity poses many challenges. This article throws light upon the six types of bioreactors used in bioprocess technology. The control system technology permits the linking of several units by ethernet, for the eventual connection to the supervision system. However, for each choice, a robust manufacturing process is critical to ensure it is scalable for these novel therapies to reach the patients. Scaleup considerations for monoclonal antibody production. Effective scaleup is essential for successful bioprocessing.
While it is desirable to keep as many operating parameters constant as possible during the scaleup, the number of constant parameters realizable is limited by the degrees of freedom in designing the largescale operation. Pdf application of different types of bioreactors in. Typical applications range from smallscale protein expression to. An in vitro cellbased potency assay has been established. Scaleup analysis for a cho cell culture process in large. In 1940s the large scale production of penicillin was a major breakthrough in biotechnology. Characterisation and scaleup considerations of singleuse bioreactors. The bioreactors provide a controlled environment for the production of metabolites which can help to achieve the optimal growth of microbes. There are numerous types of bioreactors batch, sequence, continuously stirred tanks, anaerobic contact processes.
Schematic diagrams of basic membrane bioreactor configurations yamamoto et al. The pendotech bioreactor control system is loaded with features including an easy to use graphical user interface gui. One of the first steps in designing a process is whether to use adherent or suspension cell cultures. Introductionthe function of the fermenter or bioreactor is to provide a suitableenvironment in which an organism can efficiently produce a targetproductthe target product might be cell biomass metabolite bioconversion productthe sizes of the bioreactor can vary over several orders of magnitudes. By brian lee, yas hashimura, daniel giroux, marcos sousa, joao clemente, manuel carrondo, siddharth gupta, michael mccaman, and. Dec 09, 2014 bioreactors are basically mixing vessels with a simple function. Yeast unicellular fungus more than species identified.
Bulk liquid mixing is another critical factor in the scaleup of a cell culture process. Development of an industrial biotechnology process stirred tank bioreactorsprocess integration scaleup. Carlfredrik mandenius and mats bjorkman, scaleup of cell culture bioreactors using. Adherent and suspension bioreactors for viral vector manufacturing are evolving. This chapter comprises engineering aspects of bioreactor systems design, operation, scale up developed or adapted for cultivation of mammalian cells, such as bioreactors for suspension culture. This creates the bubbles in the medium which rises up through the draught tube by buoyancy and drags the surrounding fluid up. Improving single use bioreactor design and process. This chapter comprises engineering aspects of bioreactor systems design, operation, scaleup developed or adapted for cultivation of mammalian cells, such as bioreactors for suspension culture. A schematic diagram of a 100liter reactor without the microbial support. The relative sizes of the scaling groups for this plant are shown in table r7. Keep the contents suspended and distributed without damage. The aim of process scaleup is to produce larger quantities with equivalent productivity and product quality schmidt, 2005. Some 20 years ago, the computer technology started to make advanced process control possible. Extremely compact construction saves expensive laboratory bench surface.
According to the 2016 nice insight cdmo out sourcing. The barriers to scale up in bioreactors are the following. They transition to bench scale and then up to pilot or production scale with the intent to maintain constant yield and constant product characteristics. Scale up of aerobic fermentations is often carried out on the basis of a constant oxygen transfer coefficient. Scaleup of cell culture bioreactors using biomechatronic design carlfredrik mandenius and mats bjorkman linkoping university post print n. This study shows a process for scaling up adherent vero cells from static cell factories to influenza production at 50 l scale using wave bioreactor systems and readytoprocess singleuse equipment. In bioreactors, enzymes created by microorganisms attack the plant. Market research firm markets and markets projects the us bioreactor market will increase at a compound annual growth rate of 21. This chapter comprises engineering aspects of bioreactor systems design, operation, scaleup developed or adapted for cultivation of mammalian cells, such as bioreactors for suspension culture stirredtank reactors, bubble columns, and airlift reactors, fixed bed and fluidized bed reactors, hollow fiber and membrane reactors, and, finally. This theoretical product has recently undergone up scaling to 200 l bioreactors from 5 l bioreactors in the context of moving from a successful phase ii to phase iii. Sep 30, 2014 yeast scaleup example production goal. The 2 l and 10 l bioreactors were characterized for a range of superficial gas velocity going from 5. Design, characterization, and scaleup strategy for a new singleuse productionscale bioreactor ondemand webinar.
Cell culture scaleup in stirredtank singleuse bioreactors. Mar 27, 2012 in the 2l bioreactors, do dropped to 30 % of air saturation within an hour of inoculation. Assessment of barrier containment technologies cluin. Schemes for dissolved oxygen control with sparged air in serum containing media are described, as well as mechanical breakage offoam in small and large bioreactors. Bioreactors classification and types biotech articles. Perfusion solutions can offer very costefficient scale up solutions, driving down. This scaleup procedure has been applied 11 to the data of rogovin et al. Bioreactor design 145 up through the draught tube to the head space of the bioreactor, where the excess air and the byproduct, co 2, disengage.
Jorgensen 1997 point out the importance of establishing meaningful objectives for. Section ii understanding the drinkingwater catchment. Scaling up bioreactors fluid dynamics by applying analytical techniques often reserved for largescale industrial bioreactors to. A new single use bioreactor for small scale cell cultures. Industrial scale bioreactors fermenters i series laval lab. Equipment design considerations for large scale cell culture. Setting out to isolate uncultivated deep marine sediment microorganisms, we engineered and operated a methanefed continuousflow bioreactor. Reactors may extend the full width of the contaminant plume as in the case of a. This book brings together this work in order to provide this basis. The system offers the ability to monitor and control the ph, dissolved oxygen do, and temperature with pid control.
Pdf influence of solid moisture and bed height on cultivation of. A partnership for scale up application note perfusion has emerged as a viable technology for the commercial production of biopharmaceuticals. This chapter comprises engineering aspects of bioreactor systems design, operation, scaleup developed or adapted for cultivation of mammalian cells, such as bioreactors for suspension culture stirredtank reactors, bubble columns, and airlift reactors, fixed bed and fluidized bed reactors. As a case in point, in the latephase production of guanosine, a typical phe. It makes the key point that, given the complexity of ssf systems, efficient performance of ssf bioreactors will only be achieved through. Isolation of an archaeon at the prokaryoteeukaryote interface nature. For unlimited downloads, join as a monthly or annual member.
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