During stage two, air is pumped through the mix while the microorganisms absorb the organic matter and nutrients. Before heating up to 121 c, the sterilizer was vacuumed three times. Now a number of industries have come up for the production of secondary metabolites. In chinese citric acid fermentation plants, the cultivation of bran koji. Part of the engineering commons recommended citation stoker, emily b. By brian lee, yas hashimura, daniel giroux, marcos sousa, joao clemente, manuel carrondo, siddharth gupta, michael mccaman, and. A schematic diagram of a 100liter reactor without the microbial support. Effective scale up is essential for successful bioprocessing. It also focuses on scaling up based on geometrical similarity, to better illustrate the effect of scale on different process parameters. A 1 00liter bioreactor measuring 36 em x 36 em x 80 em can be scaledup geometrically to 100 cu. This book brings together this work in order to provide this basis. Berberine, an isoquinone alkaloid was scaled up to 400 l scale by mitsui petrochemical industry, japan zenk et al.
Automated benchscale bioreactor design 3 down the organic waste and nutrients to produce an organicfree liquid. Due to the nature of these various parameters, it is not possible to maintain them all during scaleup under one set of conditions. Perfusion solutions can offer very costefficient scale up solutions, driving down. In bioreactors, the concentration of nutrients in the medium is affected mainly by absorption rate and by cell lyses. In a stirred bioreactor, mechanical agitation keeps cells and microcarriers in suspension, provides mixing to create a more homogeneous chemical environment, and creates a flow pattern that increases the. Typical scaleupdown strategies include matching the power input per volume pv or the maximum shear as represented by impeller tip speed across scales chisti 1993. Different agitation strategies are used to scaleup a process including speci. However, limitation of using t mix as scale up criteria is that it increases markedly with the.
Design, characterization, and scaleup strategy for a new. Bioreactor scaleup and oxygen transfer rate in microbial. Scaledown model development in ambr systems fujifilm diosynth. 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. Pdf a correlation between spore productivity and kla, was found for bacillus thuringiensis var. 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. Sterilization of the inlet and exit air in large bioreactors 10,000 litres can present a major design problem. Scale up in bioreactor free download as powerpoint presentation. Content introduction pilot plant design pilot plant operation requirements scale up consideration principles of similarity development milestones 3. N2 tubular and the flat plate are the two most common general designs of microalgal photobioreactors. Scaledown bioreactors have been applied in bioprocess development to study the response of microbial cell factories and other expression systems to various stressinducing concentration gradients. All you need to do is print your 3d printable paper model cut your model out and then fold glue and place your 3d paper model on your model railroad. The air that is used to lift up is sufficient to stir up the contents.
The bioreactors fermenters of the i series are highly automated production fermentation systems, available from 250 liters up to 30 m 3, fully customized. Mscs are multipotent stromal cells that can differentiate into a variety of cell types which are being investigated for tissue engineering and cellular. Anaerobic bioreactors in aerobic bioreactors, the effect of agitation is obvious due to the effect on bubble size and holdup. Pdf systematic evaluation of singleuse systems using process. This creates the bubbles in the medium which rises up through the draught tube by buoyancy and drags the surrounding fluid up. Some 20 years ago, the computer technology started to make advanced process control possible. Sartorius the univessel su is suitable for mammalian, insect and plant cell culture in scales up to two liters volume. Characteristic for all types of slurry bioreactors fig. Cell culture was originally performed in ge wave bioreactors. Pdf the choice of singleuse versus stainlesssteel systems depends on a variety of process and other parameters such as bioreactor scale, product.
Several reports on bt fermentation scaleup have been. First, the most used measuring methods are revised. 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. Scale up of cell culture bioreactors using biomechatronic design carlfredrik mandenius and mats bjorkman linkoping university post print n.
T1 scaleupbioreactor design and culture optimization. Scaledown aspects of the gluconic acid fermentation. Development and temperature gradient online monitoring of a. Certainly, you would like to follow the advice given by h. Scaledown model qualification and scale down model.
But over the course of development, biopharmaceutical companies need more material for characterization, trial runs, and finally for commercialization. Acceleron pharma has based its manufacturing platform on disposable technology for cell culture, harvest, and purification. 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. B when citing this work, cite the original article. An in vitro cellbased potency assay has been established.
Based on the power numbers and the dimensions of the impellers, an agitation rate of 1,000 rpm in ambr would generate equivalent pv as the 2l. 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. However, the micro and miniscale bioreactor systems ambr15. In 1940s the large scale production of penicillin was a major breakthrough in biotechnology. Scalingup stem cells with singleuse bioreactors and. Comparative studies on scaleup methods of singleuse bioreactors emily b. Published case studies report the scalability of su systems from microto productionscale bioreactors fernald et al. Cell culture scaleup in stirredtank singleuse bioreactors.
Pdf scaleup of bacillus thuringiensis fermentation based on. Industrial scale bioreactors fermenters i series laval lab. Stoker utah state university follow this and additional works at. Design, characterization, and scaleup strategy for a new singleuse productionscale bioreactor ondemand webinar. Scaling up bioreactors fluid dynamics by applying analytical techniques often reserved for largescale industrial bioreactors to. Biosurfactants capable of emulsifying pesticides have great potential to assist in microbial degradation of the pesticides. Mixing time t mix, defined as the period of time required for the homogeneous distribution of a small volume of pulsating material in the bulk of the liquid, was used for scale up to adjust proper mixing conditions in large vessels. In scale up of bioreactors mixing time is often used as criteria. Understanding of the mass transfer behaviour in bioreactors would result in improved reactor designs, reactor operation, and modelling tools, which are important for maximizing reaction rates. The bioreactors fermenters of the i series are highly automated fermentation systems, available from 250 liters up to 30 m 3, 8. The filters are expensive as they are difficult to make and the energy required to pass air through a. Designing of bioreactor for the production of scopadulcic. They transition to bench scale and then up to pilot or production scale with the intent to maintain constant yield and constant product characteristics.
With the scale up criterion such as similar power input per volume or o2 volumetric mass transfer coefficient kla, adequate oxygen supply and cell growth can be largely achieved. Since scaleup principles for stirred bioreactors are generally better characterized than those for other bioreactor types, such as rockertype wave. Typical applications range from smallscale protein expression to. Some scientists and engineers in biotech industry dedicate their entire careers scaling up various bioreactor processes, and each time they may encounter something new. Scaleup considerations for monoclonal antibody production. Despite success with automated model setup and identification, manual curation of. Scaleup of processes based on su bioreactors animal.
Bioreactors come in reusable or singleuse formats, with the latter increasingly available. Schemes for dissolved oxygen control with sparged air in serum containing media are described, as well as mechanical breakage offoam. Scale up studies for the production of biosurfactant in packed. 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. Researchgate is the professional network for scientists and researchers. This gen webinar will first introduce and discuss the engineering concepts of the allegro str bioreactors, a square bioreactor design with volumes of 200 l. Formal model qualification is typically carried out in phase iii runs when. Process scaleup between 3 different stirred tank bioreactors was studied.
A partnership for scale up application note perfusion has emerged as a viable technology for the commercial production of biopharmaceuticals. The control system technology permits the linking of several units by ethernet, for the eventual connection to the supervision system. Bioreactor scale up is a critical step in the production of therapeutic proteins such as monoclonal antibodies mabs. Pdf scalingup fermentation of escherichia coli for production of. A new single use bioreactor for small scale cell cultures. 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. It makes the key point that, given the complexity of ssf systems, efficient performance of ssf bioreactors will only be achieved through. Bioreactors classification and types biotech articles.
Scaleup is the procedure to transfer labbioprocesses in production. Scaleup and comparison studies evaluating disposable. Scaleup analysis for a cho cell culture process in large. In stage one, replicated wastewater is pumped into the system until the reactor is full. Scaleup of cell culture bioreactors using biomechatronic.
Carlfredrik mandenius and mats bjorkman, scale up of cell culture bioreactors using. Download your favorite free n scale 3d printable paper model pdf file for your model railroading adventure. The aim of process scaleup is to produce larger quantities with equivalent productivity and product quality schmidt, 2005. The development of genetic engineering have played a major role in. Therefore, in the scaling up of such packed beds, the bed height can be increased. The ultimate goal for process development is, however, the realization of a largescale production. Scaling up your cell cultures to bioreactors biocompare. Large scale membrane filtration is a very expensive process. Bioreactors require tradeoffs that can be systemspecific.
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. In silico prediction of largescale microbial production performance. Scaleup and scaledown methodologies for bioreactors. This scaleup procedure has been applied 11 to the data of rogovin et al. Pdf background p64k is a neisseria meningitidis high molecular weight protein present in meningococcal vaccine preparations. Laboratory and industrial bioreactors and fermenters. 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. This is the authors version of the published article. Commit your blunders on a small scale and make your profits on a large scale. Microcarrier mcbased suspension culture processes have been used to culture anchoragedependent cells in bioreactors.
However, scaleup of the process for high cell growth and productivity poses many challenges. In silico prediction of largescale microbial production. Effective scaleup is essential for successful bioprocessing. Air lift bioreactors the stirred tank bioreactors lack well defined flow of air. A practical approach in bioreactor scaleup and process. Scaleup and basis of calculation mass balance class 05 duration.