Scaleup involves the development of culture systems in stages from small scale laboratory to large scale industry. The sizes of the bioreactor can vary over several orders of magnitudes. The primary scope of this project was to investigate the scaleup capabilities of eppendorf bioblu singleuse vessels for cell culture applications from small to pilot scale. The degassed liquid then flows down the annular space outside the draft to the bottom of the bioreactor. Scale up to bench bioreactor culture from shaker flasks presented several challenges. N2 tubular and the flat plate are the two most common general designs of microalgal photobioreactors. As already indicated, the oxygen transfer rate can control the overall rate of the bioprocess, and as a consequence, it can determine the capacity of a bioreactor. The last chapter in part ii of the book scale up by c. Typical scaleup parameters such as power input per volume, kla the mass transfer coefficient, which determines the oxygen transfer rate, tip speed and mixing times are defined, and.
Scale up of aerobic fermentations is often carried out on the basis of a constant oxygen transfer coefficient. Biological engineering this study was performed to increase knowledge of oxygen mass transfer k. Stamper and cillian mccabe, bioprocess research and development, eli lilly and company bioreactor design. Scribd is the worlds largest social reading and publishing site.
It differs from the stirred tank in that mixing occurs due a rocking motion to generate waves to prevent cell settling and provide oxygenation. There are numerous types of bioreactors batch, sequence, continuously stirred tanks, anaerobic contact processes, anaerobic filters, etc. However, the scale up relationships developed should be independent of scale, i. Comprehensive study on wave bioreactor system to scale up the.
Jun 23, 2019 applikon bioreactor pdf applikon offers glass autoclavable bioreactors for cell culture applications and. The design and scaleup of biological processes is verychallenging. Pdf dynamic singleuse bioreactors used in modern liter. Scale up a4 to a3 set page size to a3 print an a3 pdf. Request pdf bioreactor design and scaleup design and selection of cell culture bioreactors are affected by cellspecific demands, engineering aspects, as well as economic and regulatory. Scale up and scaledown methodologies for bioreactors. Scale up expansion of scs with bioreactors and gmp facilities may benefit from the collaborations among biomedical researchers and bioreactor engineers.
T1 scale up bioreactor design and culture optimization. Oct 27, 2017 design, characterization, and scaleup strategy for a new singleuse productionscale bioreactor gennews. Three bioreactor sizes were selected to represent approximately 10fold scale up between steps. Request pdf scale up and scaledown methodologies for bioreactors scale up is usually complicated by the fact that bioprocesses in general are gasliquid systems, whereby the liquid phase. 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. Cooling can be provided by either making the draught. 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. Overcoming scaleup challenges during culture media development. See each listing for international shipping options and costs. Jul 14, 2014 for researchers who do plan to scale up their culture volumes, bioreactor systems use many parameters to help you keep tabs on the health of the cultures. Some scientists and engineers in biotech industry dedicate their entire careers scaling up various bioreactor processes, and each time they may encounter something new.
Comprehensive study on wave bioreactor system to scale up the cultivation of and recombinant protein expression in baculovirusinfected insect cells. Scale up 29 volumetric scale up ratio v 2 v 1 10,00080 125 impeller diameter scale up ratio d i2 d i1. In the file dialog window, browse to the desire folder, type a file name into the file name text field and click the ok button. This book does not attempt to teach the necessary modeling skills. Theory and methodology, applied science publishers, london. We recognize that many readers may not have the necessary background to set up and solve mathematical models of bioreactor performance. Usually, engineers focus on the most effective factor and take in one of the common scale up strategies. Use bioreactors by emily stoker, master of science utah state university, 2011 major professor. This design is stated to create separate cell growth and aeration zones. Considering the importance of processes scale up in all industrial activities 1, 3, 4, 9, this work presents a novel methodology for scaling up continuous reactors using i a phenomenologicalbased semiphysical model pbsm for representing the process, and ii its hankel matrix as a tool for establishing the process.
The single use rocking platform bioreactor is similar to the stirred tank, and provides a regulated environment. 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. Effective scale up is essential for successful bioprocessing. In the ideal state, the cells are growing optimally with an. The 50l and 250l subs were used for scale up and pilot runs with the optimized process a 14day fedbatch culture. Membrane bioreactor free download as powerpoint presentation. Best practices from scaleup to control in biomanufacturing, knowledge of scaleup, processing and control should be shared and documented in order to achieve and sustain operational excellence. Set up the data file path inside the bioreactor control unit software in order to store the data on the operator pc. Scaleup and oxygen transfer rate in aerobic bioprocesses. 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.
A bioreactor is divided in a working volume and a headspace volume. For overcoming the above difficulty and to facilitate scale up of plant cell culture bioreactor a design of low shear bioreactor has been reported. Bioreactors classification and types biotech articles. Cell culture scaleup in stirredtank singleuse bioreactors. G6dia is a good overview of different scaleup approaches with a few case studies. Scaleup considerations for monoclonal antibody production. For some scaleup problems, generalized correlations as shown in figures 811, 812, 8, and 814 are available for scaleup. The last part consists of two chapters devoted to sterilization and containment by a. Each method provides challenges for scaleup, but has found a place in production. However, limitation of using t mix as scale up criteria is that it increases markedly with the. The scaleup process is divided into two categories. The working volume is the fraction of the total volume taken up by the medium, microbes, and gas bubbles. Rtr has just implemented dec, 2016 the first bioreactor mixed with biochar, in a nonresearch setting, in the usa.
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. Process scale up between 3 different stirred tank bioreactors was studied. Discussions will be made on design features for bioreactors and scale up scale down considerations that need to be taken into consideration when implementing bioreactor systems. Combining theory and practice, the authors explain such leadingedge technologies as singleuse bioreactors, bioreactor simulators, and soft sensor monitoring, and discuss novel applications, such as stem cell production, process development, and multiproduct reactors, using case studies from academia as well as from industry. The primary scope of this project was to investigate the scale up capabilities of eppendorf bioblu singleuse vessels for cell culture applications from small to pilot scale. The oxygen transfer rate otr must be known, and if possible predicted to achieve an optimum design operation and scaleup of bioreactors. Scaleup and comparison studies evaluating disposable. Applikon biotechnology is a world leader in developing bioreacfor supplying advanced bioreactor systems from laboratory scale to production scale.
A summary of various strategies for bioreactor scaleup is given below. Scalability in laboratory bioreactors based on constant. Applikon bioreactor pdf applikon offers glass autoclavable bioreactors for cell culture applications and. Scale up and comparison studies evaluating disposable. T1 scaleupbioreactor design and culture optimization. Then you can print any portion of plan you want actual size.
The goal with this new practice is to not only reduce 80%90% of nitrates, but also is expected to remove 30%60% of the phosphorus from the farms agricultural runoff before it reaches the choptank river and the chesapeake bay. Process scaleup between 3 different stirred tank bioreactors was studied. Scale up in bioreactor free download as powerpoint presentation. Request pdf scale up and scale down methodologies for bioreactors scale up is usually complicated by the fact that bioprocesses in general are gasliquid systems, whereby the liquid phase. Overcoming scale up challenges during culture media. They can be conveniently classified into three major types based on the presence or absence of oxygen and requirement of stirring. A constant height to diameter ratio for the bioreactors is perhaps the simplest and most common strategy. Scaleup and scaledown methodologies for bioreactors. For this reason the oxygen transfer rate condition has been often chosen as the main criterion for scalingup. Request pdf bioreactor design and scale up design and selection of cell culture bioreactors are affected by cellspecific demands, engineering aspects, as well as economic and regulatory. However, there is much diversity in the process to be scaledup, and as such no single method can successfully handle all types of scaleup problems. A slurry bioreactor can only work properly if these three measures are balanced. 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.
Each method provides challenges for scale up, but has found a place in production. Cell culture scaleup in bioblu c rigidwall, single use. Equipment design considerations for large scale cell culture. Non stirred non aerated bioreactors are used for production of. Scaleup of cell culture bioreactors using biomechatronic. Data file 29092927 aa cell culture xcellerex xdr10 cell. Improved scaleup strategies of bioreactors springerlink.
Testing and simulation approaches for singleuse bioreactor. Bioreactor parameter optimization was conducted to attain equivalence between the two culture scales in. A constant oxygen transfer rate coefficient is usually the path for engineers, where oxygen is crucial for the fermentation and oxygen. Several of the needs in table 1 reflect the overall goal for the scaleup. In scale up of bioreactors mixing time is often used as criteria. Scaleup of cell culture bioreactors using biomechatronic design. Power input measurements in stirred bioreactors at laboratory. Scale up and oxygen transfer rate in aerobic bioprocesses. Design, characterization, and scaleup strategy for a new singleuse productionscale bioreactor gennews. Scale up involves the development of culture systems in stages from small scale laboratory to large scale industry. Development of an industrial biotechnology process using. The last chapter in part ii of the book scaleup by c.
Bioreactor scaleup and oxygen transfer rate in microbial. Design, characterization, and scaleup strategy for a new. The microbial cell few mm3, shake flask 100 ml, laboratory fermenter 1 50 l, pilot scale 0. Despite challenges, the understanding of the mechanisms under the regulation of sc fate will guide improvement of the sc expansion using bioreactor.
Best practices from scale up to control in biomanufacturing, knowledge of scale up, processing and control should be shared and documented in order to achieve and sustain operational excellence. The oxygen transfer rate otr must be known, and if possible predicted to achieve an optimum design operation and scale up of bioreactors. An overview of fermenter and the design considerations to. Pdf application of different types of bioreactors in. Three bioreactor sizes were selected to represent approximately 10fold scaleup between steps. Bioinstrumentation and controls utilized in process systems are important in reactor design and operation. Scale up to 1,000l perfusion in a disposable stirred tank bioreactor. G6dia is a good overview of different scale up approaches with a few case studies. Data file 29092927 aa cell culture ge healthcare life sciences xcellerex xdr10 cell culture bioreactor system the singleuse xcellerex xdr10 is a flexible, stirredtank bioreactor system suitable for use in process development, smallscale production, and process troubleshooting fig 1. Comprehensive study on wave bioreactor system to scale up. For each reactor configuration,the appropriate process conditions depend on parameters such as the reactor scale,particle size distribution,slurry density,slurry viscosity,oxygen demand of the biomass, and the solids hold up kleijntjens, 1991. Instead, it is calculated based on average airwater correlations, and is intended to show how the pv and u s will tend to vary upon scaleup if effort is not made to.
Thus, the equipment used for the experiments should be selected or designed to ensure artifacts, for example, due to poor mixing are not inadvertently introduced into the results. At this stage, it is important to ensure that you have optimized cell growth, viability, protein quality, and bioreactor automation parameters before eventually harvesting the cells and initiating the purification process. Considering the formation of cellular clusters at low rocking speeds run 1 and the oxygen demands of infected tn5 cells in different culture media, another set of experiments were conducted for protein expression in 10 l and 50 l cellbags to not only verify the applicability of scale up based on the oxygen demand in wave bioreactor, but also. Sep 12, 20 each method provides challenges for scale up, but has found a place in production.
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. Application of different types of bioreactors in bioprocesses. Free newsletter sign up free newsletter subscribe sign up to our free newsletter and get the latest news sent direct to your inbox. For researchers who do plan to scale up their culture volumes, bioreactor systems use many parameters to help you keep tabs on the health of the cultures. The scale up process is divided into two categories. Open the settings tab page and hit the folder symbol next to the data file location text field. The stirred tank bioreactor str typically, the working volume will be 7080% of the total fermenter volume. Parameters to be considered for scaleup of biotechnologyproducts are. For this reason the oxygen transfer rate condition has been often chosen as the main criterion for scaling up. Most fullscale fermenters have a pv level of about wl, while many pilot fermenters have a pv in the range of 510 wl. Discussions will be made on design features for bioreactors and scaleupscaledown considerations that need to be taken into consideration when implementing bioreactor systems. Download acrobat pdf file 640kb recommended articles citing articles 0 references. This work studies the scalability between 3 different volumes of lab scale bioreactors, 500 ml, 3 l and 15 l.
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