Moreover, the development of singleuse bioreactors rapidly increased after the first wave bioreactor was introduced. Bed reactor, bubble column, hairy roots, orbitally shaken, reusable, singleuse, stirred, suspension cell culture, vertically oscillating disk, wavemixed contents 1. The supbr consisted of a standard 2 l biostat cultibag sartorius stedim biotech. Use of orbital shaken disposable bioreactors for mammalian. Orbitally shaken bioreactors osrs are based on the disposable technology single use bioreactors and are therefore very flexible. Recently, orbitally shaken bioreactors at scales from a few mls to 2000l have been explored for the cultivation of mammalian cells and are considered to. Calculation of the liquid distribution influence of filling volume and shaking frequency results of the liquid distribution model. Appliflex, rocking bioreactors from 10 to 50 liter, hyclone sub stirred tank bioreactors in the range of 66 to 2,700 liter total volume, atmi pad square bioreactors in the range of 25 to 2,500 liter total volume and atmi icellis nano bioreactors for cultivating anchorage dependable cells. Such single use cultivation systems include wavemixed and orbitally shaken bioreactors whereby the medium containing the cells is efficiently mixed by rocking or shaking the bag, which continuously renews the medium surface, providing bubblefree surface aeration.
Recently, orbitally shaken bioreactors osrs is becoming increasingly used for mammalian cells cultivation in suspension. Orbitally shaken bioreactorsviscosity effects on flow characteristics orbitally shaken bioreactorsviscosity effects on flow characteristics ducci, andrea. In this regard orbital shaking of a single use photobioreactor supbr bag could provide a number of advantages as illustrated in fig. This work aims to improve our understanding of these bioreactors by studying their engineering principles such as mixing, the gas transfer and the hydrodynamics in the frame of mammalian cell culture. Orbitally shaken bioreactorsviscosity effects on flow. Bioreactors 5l cylindrical glass bottles duran schott glass, mainz, germany were equipped with a vented cap having a 1.
Recently, the use of an orbitally shaken single use bag bioreactor has been described 15 that can be used with a standard shaking incubator multitron cell with shakerbag option from infors ag. Request pdf orbitally shaken singleuse bioreactors orbitally shaken singleuse reactors are promising reactors for upstream processing, because they. In contrast to largescale stirredtank bioreactors, shaken flasks are usually operated in probeindependent bioprocesses, i. Singleuse bioreactors have reached the big time biopharm. Applikon offers several types of single use bioreactors. Bayshake bioreactor 35 and orbitally shaken singleuse bioreactors current. Orbshake bioreactors for mammalian cell cultures infoscience. Request pdf orbitally shaken singleuse bioreactors orbitally shaken singleuse reactors are promising reactors for upstream processing, because they fulfill three general requirements for. On the measurement and scaling of mixing time in orbitally. Bioreactor, orbshake bioreactor contain no moving parts in the bag. Mode decomposition and lagrangian structures of the flow dynamics in orbitally shaken bioreactors. Orbitally shaken bioreactors osrs is one of important bioreactors for mammalian cells cultivation in suspension, especially for the screening of valuable microorganisms and in basic bioprocess. Novel orbital shake bioreactors for transient production. The sb50x can be used in research, process development or production.
For this reason, efforts are being made in the industry to develop more effective, flexible and costefficient bioprocesses. Shaken bioreactors are extensively used in the early stages of bioprocess development, with micrometer plates 24, 48, 96 or 384 wells being advantageous for processing a large number of experiments in parallel, while shaken flasks 25 ml 6 l are the most widely used type of orbitally shaken reactors ors as they offer a costefficient. Smaller orbitally shaken bioreactors may provide inoculum for the larger bioreactors, e. The bioreactors are applicable for scale up processes or can serve as independent pilot or production reactors. Besides stirred bioreactors, which closely mimic standard bioreactors, wavemixed and orbitally shaken bioreactors are also used in industry. Thermo scientific offers a range of bioreactors perfectly suited for mammalian cell culture and microbial fermentation applications that span process development, clinical trials, and largescale commercial biomanufacturing. Based on the milestones in the development of subs, it focuses on the three most often applied types.
Singleuse glucose sensor for singleuse bioreactors eurostar. Scalable production of aav vectors in orbitally shaken hek293. Orbitally shaken singleuse bioreactors, by wolf klockner, sylvia diederichs, jochen buchs. Propagation of hairy roots delivering bioactive compounds. Scaling up bioreactors fluid dynamics march 2018 sketch of the piv system setups used to measure the velocity field on a vertical and b horizontal planes. Adenoassociated virus aav vectors are currently among the most commonly applied for in vivo gene therapy approaches. Orbitally shaken singleuse bioreactors connecting repositories. Second, the liquid distribution induced by orbital shaking is. A novel shakerbag option for multitron cell shaking incubators allows a rapid increase in working volume from small tubespin bioreactors or shake flasks up to 10 l, thus offering a simple and cost.
Cho and hek293 cultivation and transfection in singleuse. Linear damped interfacial wave theory for an orbitally. Recently, orbitally shaken bioreactors at scales from 50 ml to 1,000 l have been explored for the cultivation of mammalian cells and are considered to be attractive alternatives to conventional stirredtank bioreactors because of increased flexibility and reduced costs. Use of orbitally shaken singleuse bioreactors characterization of orbitally shaken singleuse bioreactors for plant cell cultivation 1 raven n, klockner w, anderlei t, rasche s, kuhn c, buchs j, schillberg s. Request pdf orbitally shaken singleuse bioreactors orbitally shaken single use reactors are promising reactors for upstream processing, because they. Mixing, orbitally shaken bioreactor, viscosity, circulation time, dissipation rate, kinetic energy, uid mechanics. A summary from the manufacturers and user perspective. Excellgenes platform includes no moving parts, low shear force, and high gas transfer. Sorry, we are unable to provide the full text but you may find it at the following locations. Plant cell bioreactors encyclopedia of life support systems. However, the suitability of osrs for cells culture in large scale is still under development. A novel shakerbag option for multitron cell shaking incubators allows a. The scaleup process from an erlenmeyer flask shaken on an orbital platform to an orbitally shaken singleuse bioreactor sb10x, 12 l. Third, the scaleup from smallscale systems, where shaken bioreactors are commonly applied, is simple and has been successfully proven up to the cubic meter scale.
Such singleuse cultivation systems include wavemixed and orbitally shaken bioreactors whereby the medium containing the cells is efficiently mixed by rocking or shaking the bag, which continuously renews the medium surface, providing bubblefree surface aeration. In this regard orbital shaking of a singleuse photobioreactor supbr bag could provide a number of advantages as illustrated in fig. Influenza a virus production in a singleuse orbital. The aim of the pharmaceutical industry is to manufacture complex therapeutic proteins or biologics to treat human diseases. Mass propagation of helianthus annuus suspension cells in orbitally shaken bioreactors. Orbitally shaken bioreactors viscosity e ects on ow. Flow characterization and transition in orbitally shaken bioreactors. An approach for scaleup of geometrically dissimilar orbitally shaken single use bioreactors chem. A highquality product begins with efficient upstream process equipment.
However they have some disadvantages, orbitally shaken single use reactors are. During the past 10 years, singleuse bioreactors have been well accepted in modern biopharmaceutical production processes targeting highvalue products. Analyzing the suitability of a baffled orbitally shaken. Orbitally shaken bioreactors osbs utilize the same hydrodynamic principles that define the success of smallerscale cultures, which are developed on an orbitally shaken platform, and can simplify scaleup. A working volume from 15 litres up to 50 litres ensures easy scaleup from microtiter plates to shaking flasks. The engineering of a scalable disposable orbitally shaken. Furthermore, these data are often generated using a number of different methods, making comparisons. Apr 20, 20 third, the scaleup from smallscale systems, where shaken bioreactors are commonly applied, is simple and has been successfully proven up to the cubic meter scale. Ducci university college london, department of mechanical engineering, torrington place, london, wc1e 7je, uk a. Disposable orbitally shaken bioreactors are a promising alternative to stirred or wave. However, orbitally shaken singleuse reactors are only suitable for certain applications such as cultivating animal or plant cells with low oxygen demand. Engineering characteristics and scaling up, by christian loffelholz, stephan c. This approach allows us to calculate explicit formulas for the phase shifts between wave and shaker which are practically important for the mixing efficiency in orbitally shaken bioreactors.
Influenza a virus production in a singleuse orbital shaken bioreactor with atf or. Orbitally shaken singleuse bioreactor for animal cell. This work describes the use of an orbitally shaken, single use bag for phototrophic microalgae cultivation. Ten years ago, manufacturers were still warming up to singleuse bioreactors, which were mainly rockingbagbased solutions. Scalable production of aav vectors in orbitally shaken. Ducci, microcarriers suspension and flow dynamics in orbitally shaken bioreactors, chem. The sb10x is an orbital shaken benchtop bioreactor system for the cultivation of human, mammalian. Resonance dynamics is described using eight dimensionless numbers, revealing a variety of different effects influencing the forced wave amplitudes. Large shaken disposable bioreactors have working volumes of 2l12l sb10 b,10l50l sb50 c, 40l200l sb200d and 200l2500l sb2500e. Transient gene expression in these two cell lines has also been performed in wave bioreactors up to the 20 l scale , 14. A set of modal equations for irrotational waves is formulated that we complement with viscous damping rates to incorporate energy dissipation. Singleuse disposable technologies for biopharmaceutical. Hydrodynamic stress in orbitally shaken bioreactors bmc. Fluid dynamics and mixing behavior in orbitally shaken.
Singleuse orbitally shaken bioreactors osrs consist of a shaker, a structural support to which a disposable bag conforms to and all ancillary connections and controllers. Efficient scale up from lab scale to production scale using orbitally shaken. This chapter aims to give an overview of instrumented single. This work describes the use of an orbitally shaken, singleuse bag for phototrophic microalgae cultivation. General theoretical background of plant cell and tissue cultures and their processes 2. Q wave mixed and orbitally shaken single use photobioreactors.
Orbitally shaken bioreactors are now available up to a 200 liter working volume developed by kuhner ag in. An approach for scaleup of geometrically dissimilar. Orbitally shaken singleuse bioreactors springerlink. Adolf kuhner ag, user manual orbshake bioreactor sb10x. Scaleup production of pharmaceutical proteins in plant cell suspensions with orbitally shaken disposable bioreactors. Standardized cell culture test for the early identification of critical films for cho cell lines in. For the cylindrical orbital shaken bioreactors, high volumetric oxygen transfer rates and short mixing times can be achieved depending on the bioreactor size and the shaking frequency. Conclusion and outlook glossary of terms abbreviations bibliography biographical sketches summary. An initial approach for scaling up geometrically dissimilar orbitally shaken bioreactors is presented. Orbitally shaken singleuse bioreactors request pdf. The sb50x is an orbital shaken bioreactor for the cultivation of human, mammalian and plant cells in a disposable bag. Phase resolved piv measurements were carried out to assess the flow dynamics occurring in orbitally shaken bioreactors of cylindrical geometry when working fluids of increasing viscosity are considered.
The evaluation of vectors during clinical development requires the production of considerable amounts of highly pure and potent vectors. Orbitally shaken flasks are commonly used at an early stage of bioprocess development with mammalian cells. Orbitally shaken bioreactors for mammalian cell culture. Disposable bioreactors for plant liquid cultures at litre scale eng.
Engineering characterisation of a shaken, singleuse. Orbitally shaken singleuse reactors are promising reactors for upstream processing, because they fulfill three general requirements for singleuse equipment. Characterization and optimization of singleuse bioreactors and. Biochemical engineering and cell culture technique zhaw.
Orbitally shaken bioreactors orbitally shaken single use bioreactors 40 rely on the rotating motion of the culture vessel around a central axial shaft to provide mixing and oxygen transfer from the head space into the culture. Chodg44 cells were cultivated in suspension in 1l bottles as described in. Production scale osrs with singleuse bags, employ the agitation principle of shaken flasks and microwell plates, providing a homogeneously singleuse upstream scaleup. Recommendations for the engineering characterization of. For the most part, cell and genetherapy processes have, to date, been conducted in existing singleuse bioreactors. An approach for scaleup of geometrically dissimilar orbitally shaken singleuse bioreactors chem. Here, we set up a scalable process for aav production, using orbitally shaken bioreactors and a fully characterized suspensionadapted cell.
Moreover, the development of single use bioreactors rapidly increased after the first wave bioreactor was introduced. Successful integration of online monitoring systems for power input and oxygen transfer in orbitally shaken bioreactors. On the basis of design and construction bioreactors may be 1. These encouraging results represent the basis for scalingup the tips approach to the orbitally shaken sb50x in the future. The benefits relating to cleaning and validation were clear, but their use as bioreactor vessels was still new, and stainless steel systems up to 20,000 l in scale were still needed. Propagation of hairy roots delivering bioactive compounds for. Introduction shaken bioreactors are extensively used in the early stages of bioprocess development, with micrometer plates 24, 48, 96 or 384 wells being advantageous for processing a. This is an open access article, distributed under the terms of the creative commons attribution. A new orbitalmixed 2l12l single use bioreactor for cell. However, process engineering data for these bioreactors, including volumetric mass transfer coefficients, mixing times and power inputs, are still limited. Orbitally shaken bioreactors viscosity effects on flow.
An approach to quality and security of supply for singleuse bioreactors. Nextgeneration singleuse bioreactor technology and the future of biomanufacturing. Linear damped interfacial wave theory for an orbitally shaken. Driven by the commercial success of recombinant biopharmaceuticals, there is an increasing demand for novel, costeffective mammalian cell culture bioreactor systems for the production of biologicals requiring mammalian protein processing. However, orbitally shaken single use reactors are only suitable for certain applications such as cultivating animal or plant cells with low oxygen demand. Orbitally shaken bioreactors osrs is one of important bioreactors for mammalian cells cultivation in suspension, especially for the screening of valuable microorganisms and in basic bioprocess development experiments.
The bioreactors are available in four different sizes with varying working volumes. Although these bag bioreactors are characterized by reduced foam formation and less flotation in comparison to stirred systems, their power input is limited. Appraisal of the mixing performance of singleuse shaken. These bioreactors, which are made of rigid or flexible plastic materials, differ from their traditional counterparts in terms of their working principles, mix ing and power input. Despite recent progress of shaken bioreactor platforms, with the development of optical sensors and control loops to improve automation in millilitre scale bioreactors, the number of publications which address scaling updown aspects of shaken bioreactors is very limited.
Mass propagation of helianthus annuus suspension cells in. Description of most commonly used types of plant cell bioreactors 3. The orbitally shaken bioreactors from kuhner are ideally suited for the cultivation of mammalian and human cell cultures as well as insect and plant cells. Pdf dynamic singleuse bioreactors used in modern liter and m. Recently, orbitally shaken bioreactors at scales from 50 ml to 1,000 l have been explored for the cultivation of mammalian cells and are considered to beattractive alternatives to conventional stirredtank bioreactors because ofincreased flexibility and reduced costs. Pdf dynamic singleuse bioreactors used in modern liter. Use of the multitron cell incubator shaker for plant cell. The bioreactor portfolio offers options from 1 l glass bioreactors to 2,000 l single use bioreactors. The sb200x is an orbital shaken bioreactor with a working volume from. The cylindrical vessels of the bioreactors accept singleuse gammasterilized 3d. The manufacture of biologics requires a significant amount of financial and infrastructure resources. Singleuse bioreactors and microcarriers scalable technology for cellbased therapies.
Besides stirred and wavemixed bioreactors, orbitally shaken systems, such as mi. Mode decomposition and lagrangian structures of the flow. Last called such as sartorius stedims biostat cultibag rm operate with a twodimensional cultivation bag, which is made from plastics and moved on a rocker. School of life sciences and facility management, institute of biotechnology, zurich university of. Orbital shaken benchtop bioreactor for singleuse bags. Singleuse bioreactors such as the icellis allow rapid process qualification, implementation, and commercialization, providing the speedtomarket that nextgeneration biologic manufacturers need, she states. Dynamic singleuse bioreactors used in modern liter and m3 scale biotechnological processes.
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