Chondrogenic potential of hascs expanded in flask or in a. Hollow fiber based technologies in general are used in many applications, from tangentialflow filtration to prokaryotic biofilms in wastewater treatment. Cd63 and alix were greatly enriched from the bioreactor compared to flask culture. A unique hollow fiber multiple bioreactor system and method for the propagation of cells and the production of various cell propagation products is described. Interest in hollowfiber perfusion bioreactors is growing.
This manuscript describes the setup and operation of a hollow fiber bioreactor system for in vivolike mammalian tissue culture. Schematic representations of five available strategies for increasing volumetric productivity in. Application of submerged hollow fiber membrane in membrane. The hollow fiber bioreactor for the reasons outlined above, there is currently tremendous interest in 3dimensional cell culture systems. Hollow fibre hollow fiber configurations comprise one of the three main configurations for membrane bioreactor technology. The hollowfiber membrane systems have been used as bioreactors years ago due to the advantages that present, such as.
Modelling nutrient transport in hollow fibre membrane. Pdf municipal wastewater treatment using a hollow fiber. This article throws light upon the six types of bioreactors used in bioprocess technology. Airlift bioreactors are tower reactors for largescale aerobic cultures where the mixing of the culture broth is done by the inserted gas via an airlift pump fig. In the bubble column bioreactor, the mechanical impeller is exchanged with raising bubbles, which, in the case of an aerobic fermentation will anyhow be required and to the bene. Desirable properties of bioreactors bioreactor simplicity of design continuous operation w narrow distribution time large number of organisms per unit volume prof. The petri dish is the simplest immobilized bioreactor. The hek293 bioreactor culture yielded an equivalent number of exosomes per harvest as 70 t225 flasks. Without coupling with the membrane filtration, the complete mix bioreactor may only be suitable. Jun 01, 2001 the bioreactor is rotated to provide gentle mixing of fresh and spent nutrient without inducing shear forces that would damage the cells.
The functional behavior of cells in culture can be improved by culturing in more in vivolike 3dimensional culture environments 1621. Application of submerged hollow fiber membrane in membrane bioreactors. In many ways, the hollow fiber bioreactor may be considered the original modern 3 dimensional. Hollow fiber is one of the most popular membranes used in industry. The culture chamber of a hollowfiber bioreactor comprises a number of hollow fibers bundled together and encased within a cylindrical cartridge. Fewer revalidations and process changes can save time and money, delivering your cellular product to market with greater speed and efficiency. The main shortcoming of the stirred bioreactor, its mechanical agitation, is solved in other bioreactor designs. Hollow fiber bioreactor technology for tissue engineering. An automated cell culture platform, such as the quantum system, allows you to lock in a reproducible cell culture process early, which can reduce revalidation efforts later. The bioreactor ballprobe comes with a stainless steel protective cap that shields the internal optics of the probe during autoclaving and storage.
The high mechanical strength of the ptfe membrane made it possible to increase the effective length of the membrane fiber from 2 to 3 m. Fibercell systems hollow fibre bioreactor for high density. Production of exosomes in a hollow fiber bioreactor. Cells suspended in tissue culture medium are inoculated into the extra. Membrane life is a significant component of operating costs. There are different types of membranes available for use in mbrs. Hollow fiber bioreactor technology for tissue engineering applications article pdf available in the international journal of artificial organs 391 february 2016 with 665 reads.
Hollow fiber bioreactors for in vivolike mammalian tissue. A technologically advanced highgrossfiltration rate hydrophilic polysulfone fiber with a molecular weight cut off mwco of 20kd is specified. It is a wellestablished system for the production of secreted proteins from hybridoma, chinese hamster ovary cells cho, human embryonic kidney hek 293 and other. This pump injects compressed air at the bottom of the discharge pipe, which is immersed in the liquid. Definitions 1 bioreactor is a vessel in which a chemical process is carried out which involves organisms mainly microbesviruses or bacteria, fungi and yeasts traditionally designated as fermenters or biochemically active substances enzymes, e. The complete mix anaerobic bioreactor is a conventional anaerobic bioreactor.
Us5656421a multibioreactor hollow fiber cell propagation. Energy reduction of a submerged membrane bioreactor using. Wilke hollow fiber membranes have been used for more than a decade to cul ture mammalian cells and immobilize enzymes. In these dynamic culture platforms, a hollow, porous fiber membrane with diverse filtration rates, fabricated from. Pirrone c 2017 chondrogenic potential of hascs expanded in flask or in a hollow fiber bioreactor j stem cell res med, 2017 doi.
Hollow fiber reactors reduce cost, scaleup concerns. Simultaneous fluid flow through lumens of hollow fibers in bioreactors is maintained constant across multiple bioreactors so production is maintained essentially constant. More recently, hollow fiber bioreactors have shown encouraging potential for culturing. In order to more closely approximate in vivo cell growth conditions, richard knazek developed the hollow fiber bioreactor hfbr in 1972 1. Highdensity cell growth is shown in extracapillary space. Operation of a submerged hollow fiber membrane bioreactor for wastewater treatment on meeting reclamation criteria. Production of recombinant proteins and monoclonal antibodies. The bioreactors described here are seeded at a 35fold higher cells density cellcm 2 than used in 2d tissue culture plastic for a 7 day culture. The hfbr system is a highdensity, continuousperfusion culture system. These bioreactors are commonly cylindrical, ranging in size from litres. Hollow fiber bioreactors have been in use for more than 30 years for the production of secreted proteins and antibodies from mammalian cells. C3s hollow fiber bioreactor systems are a solution to both goals. Monitoring of cell viability and cell growth in a hollow fiber bioreactor by use of the dye alamar blue.
For adherent cell types, hfbs offer an in vivolike microenvironment as each fibre replicates a blood capillary and the mass transfer rate across the wall is independent from the shear stresses experienced by the cell. Hollow fiber bioreactor systems increase cell culture yield one of the most important advances in the field of cell biology came in the early 20th century, with the discovery that plant and animal cells could survive and even replicate outside the living organism. Benjamin freeman1, naomi jones1, craig bartels1, shinya sunano2, takanori itonaga3. Design of bioreactors for plant cell and organ cultures. Instrumentation and process control perfusion bioreactors. High in c internal helical coil and d internal baffle coil for large reactors. A bioreactor refers to any manufactured device or system that supports a biologically active environment. The hollow fiber system was run in batch mode to mimic the method used for the cl with bd mab medium. The large scale immobilized bioreactors are used for commercial manufacturing of metabolites. Hollow fibre membrane bioreactors hfb provide a novel approach towards tissue engineering applications in the field of regenerative medicine. Hollow fiber bioreactors are the focus of scientific research aiming to mimic physiological vascular networks and engineer organs and tissues in vitro. Jul 09, 2016 however, implementing smallscale hollow fiber bioreactors for culturing mammalian cells can save a lot of time and money, and is especially useful for harvesting large quantities of secreted protein. A hollow fiber bioreactor is a 3 dimensional cell culturing system based on hollow fibers, which.
Highlights membrane bioreactors mbr have total installed capacity exceeding 5 million m3d. Comparison of cell growth in tflasks, in micro hollow fiber. Graphical representation of tissue engineering using hollow fibers as scaffolds. A hollow fiber bioreactor is a 3 dimensional cell culturing system based on hollow fibers, which are small, semipermeable capillary membranes arranged in parallel array with a typical molecular weight cutoff mwco range of 1030 kda. Hollow fiber membrane life in membrane bioreactors mbr. The system is designed to fit onto the shelf of a standard co 2 incubator and is simple enough to be setup by any competent cell biologist with a good understanding of aseptic technique. Cellmax cellmax duo hollow fiber cell culture system. Here we consider only their use in the culture of animal cells, referring to this as hollow fiber perfusion bioreactor hfpb technology. Pdf monitoring of cell viability and cell growth in a. This book discusses the applications of biological kinetics and thermodynamics. 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.
Highlights membrane bioreactor was used for treating high cod tapioca wastewater. The use of cell cultures within a hollow fiber bioreactor could address many of these limitations and produce a continuous source of highly concentrated evs without contamination from serum evs, and that are suitable for downstream applications. The structure of that bundle is such that the figure 1. Schematic representations of five available strategies for increasing volumetric productivity in adherent cell culture a. Membrane bioreactor mbr technology, which is a combination of biologicalactivated sludge process and membrane filtration is widely spread, and accepted in recent years for the treatment of many types of wastewaters, while the conventional activated sludge cas process.
Cells grow on and around the cartridge fibers at densities of greater than 1 x 10 8 per ml. Apr 05, 2011 the production of secreted products from mammalian cells such as recombinant proteins and monoclonal antibodies is generally performed in the laboratory by standard flask, roller, or spinner culture. Instead, it will focus on suggestions that should be applicable to a. To study the solubilization of corn fiber fermentation with the addition of ll55 or its cfe, phcontrolled bioreactor fermentations of 40 gl fiber enriched corn bran were conducted table 5. Hollow fiber bioreactors introduction achieving high cell densities and reducing the costs to produce biologics are desirable but not always simple or inexpensive goals. Use of a hollow fiber bioreactor to collect extracellular. Hollow fiber bioreactors are the ultimate solution to achieving highdensity, continuous culture. Harvest large quantities of secreted protein with hollow. The hollow fiber bioreactor disposable set is a highly efficient bioreactor configuration suitable for small scale biomass or protein production. Due to their high level of cellular organization and specialization, samples constructed in the bioreactor more closely resemble the original tumor or tissue found in the body. Biological cultures are most commonly performed in flasks, roller bottles or spinners. Bioreactor an apparatus usually jacketed cylindrical ss vessel for growing organisms such as bacteria, viruses, or yeast that are used in the production of pharmaceuticals, antibodies, or vaccines, or for the bioconversion of organic wastes under optimum conditions of gas air, oxygen, nitrogen. These hollow fiber membranes are often bundled and housed within tubular polycarbonate shells to create hollow fiber bioreactor cartridges.
On the basis of the microbial agent used, the bioreactors can be classified into those based on living cells. Hollow fiber membrane bioreactor for cod biodegradation of tapioca wastewater. Membrane life was determined by analysis of all zeeweed mbr installed in north american since their introduction in 1996. The advantages of hollow fiber bioreactors in cell culture. Disposable set hollow fiber bioreactor semipermeable membrane upscaling made easy the porous surface structure of the membrane provides a more invivo like culture environment with excellent nutrient supply. Vicaria department of chemical engineering, faculty of sciences, university of granada, 18071 granada, spain and it is possible perform a simple scaling using several units in parallel form, obtaining high productivities. They include moving bed fibrous bed packed bed membrane 4. Use of hollow fiber systems for rapid and direct scale up of. Production of exosomes in a hollow fiber bioreactor john j s cadwell, president and ceo, fibercell systems inc introduction exosomes are small lipid membrane vesicles 80120 nm of endocytic origin generated by fusion of cytoplasmic endosomal multivesicular bodies with the cell surface. Removal of chemical oxygen demand cod and biochemical oxygen demand bod 5 was investigated.
Since there are a wide variety of different bioreactors being used for mammalian cell culture, this document will not address specific bioreactor models. Advantages of hollow fiber bioreactors from fibercell systems. The reason for this lies in the interesting features of this bioreactor type, including excellent mass transport properties. The flns murine hybridoma cell line was simultaneously inoculated at 2 million cells per ml in a cl and the maximizer hollow fiber bioreactor system, a 21fold theoretical scale up over the cl. The hollow fiber usually has a membrane coated on the outside of a porous fiber support as shown in fig. Jun 14, 20 demonstrating the first steps in setting up a hollow fiber bioreactor for preculture. Temperature control heat transfer heat transfer surface area. The key benefit of hollow fiber bioreactor hfbx technology is the high cell density attained 10 8 cellsml through the use of continuous media perfusion to. A bioreactor equipped with hollow fiber microfiltration membranes was applied for wastewater treatment.
Hollow fiber bioreactors for in vivolike mammalian tissue culture. Hollow fiber bioreactors consist of a bioreactor, an oxygenator, a flow path, and a recirculation pump. Development of a thermophilic coculture for corn fiber. The hollow fiber bioreactor hfbr is a highdensity continuousperfusion culture system consisting of a cartridge containing thousands of semipermeable hollow fibers in a parallel array within a tubular housing. To address the above issues, and in particular, the limitations of the current bone defect management mechanisms, recent work in tissue engineering has been attempting to develop a hollow fibre membrane bioreactor hfmb that could overcome this diffusion limitation. Tubular membranes were available for laboratory use as early as the 1920s and were first used in industrial applications in the 1960s. Cells suspended in media are introduced into the space of the cartridge out side the fibers known as the exctracapillary space. Hollow fiber bioreactors, for example, feature a fibrous membrane structure 50. Hollow fiber cell culture is the only means to culture cells at in vivolike cell densities. Cellmax duo hollow fiber cell culture system cellmax duo hollow fiber cell culture system cellmax, hollow fiber cell culture technology initiation of culture in the cellmax, cells are grown on and around a network of artificial capillaries encased in a cartridge shell. Electrically conductive, graphenecoated, hollow fiber porous membranes were used as cathodes in anaerobic electrochemical membrane bioreactors anembrs operated at different applied voltages 0.
Graphenecoated hollow fiber membrane as the cathode in. Wave bioreactor systems, wave mixer, tubing sealers and welders, hollow fiber and normal flow filters, prepacked chromatography columns, and akta ready chromatography system with a disposable flow path, as well as the assemblies and connections in between. Filtration principles, operation, and membrane fouling desalination 283 2011 39 contents lists available at sciencedirect desalination j o u r n a l h o m e p a g e. Polymeric hollow fiber membranes for bioartificial organs and tissue. Inoculating cells into a fibercell systems hollow fiber bioreactor. The hollow fiber bioreactor and cell cocultivation. Hollow fibre hf membranes are normally vertically oriented with the aerators integrated either with the module or frame. Airlift bioreactors an overview sciencedirect topics. The culture chamber of a hollow fiber bioreactor comprises a number of hollow fibers bundled together and encased within a cylindrical cartridge.
Use of hollow fiber systems for rapid and direct scale up. The full text of this article is available as a pdf 151k. The element is most commonly referred to as a module. A fibercell systems hollow fibre bioreactor enables the continuous culture of large numbers of cells at high density. Jul 27, 2014 hollow fibre membrane bioreactors hfb provide a novel approach towards tissue engineering applications in the field of regenerative medicine. The array of automated multiparallel mini bioreactors and classic benchtop bioreactors supports fast and reliable development and characterization of your processes throughout all phases. The onset of biofouling was delayed and minimized in rectangular reactors operated at 0. May 26, 2016 this manuscript describes in detail the setup and operation of a hollow fiber bioreactor system for the in vivolike culture of mammalian cells. Setting up a fibercell systems hollow fiber bioreactor. Nov 12, 2015 hollow fibre membrane bioreactor system. Jun 12, 2012 figure 5 placental cells harvested from the hollow fiber bioreactor and placed in a t75 flask. Only recently have we begun to understand how culture conditions can dramatically affect protein quality.
Hollow fiber bioreactors smallscale systems hf primer excellent alternative to tflasks, spinners, roller bottles, ascites, wave, celligen runs weeks to months yes uses singleuse disposables yes culture suspension or adherent cells yes bioreactor culture volume and size 80 ml,1. Disposable singleuse bioreactors for mammalian cells. In one case, a bioreactor is a vessel in which a chemical process is carried out which involves organisms or biochemically active substances derived from such organisms. After three days of flask culture, the adherent cell layer is well established and embryoid bodies are well defined. In this study, we modified a polytetrafluoroethylene ptfe hollow fiber membrane element used for submerged membrane bioreactors mbrs to reduce the energy consumption during mbr processes. In many ways, the hollow fiber bioreactor may be considered the original modern 3 dimensional cell. Anaerobic membrane bioreactors anmbr for wastewater. Wash the cells by adding 10 ml phosphate buffered saline pbs, aspirate, then add 3 ml 0. C3 has four hollow fiber bioreactor hfbrx systems to address a wide range of production applications. Wenten department of chemical engineering, itb, jl. Seamless transfer to pilot and production scale bioreactors are ensured by sartorius thorough understanding of bioreactor design and scaleup principles.
The flns murine hybridoma cell line was simultaneously inoculated at 2 million cells per ml in a cl and the maximizer hollow fiber bioreactor system, a. Estimated membrane life of the current product should be greater than 10 years. Hollow fibre membrane bioreactors for tissue engineering. Hollow fiber bioreactors also provide a tremendous amount of surface area in a small volume. The potential application of hollow fiber bioreactors to. Conversion of bioreactors to continuous perfusion using. Filtration principles, operation, and membrane fouling ultrafiltration hollow fiber membrane bioreactor mbr treating oil refinery wastewater. Organized into seven chapters, this book begins with an overview of the design of biological reactors that involves determining operating conditions, sizing the reactor, controlling. Bioreactors classification and types biotech articles. Bioreactor design fundamentals presents the development in the bioreactor field. Conclusions the use of membrane bioreactors has grown exponentially over the past two decades following the. Pros and cons of different expansion systems for manufacturing of. The hollow fiber bioreactor system delivers media to the cells in a manner akin to the delivery of blood through the capillary networks in vivo. Low in a external jacket and b external coil for small reactors 2.
Table 1 introduces many of the growing applications. Pdf optimizing t cell expansion in a hollowfiber bioreactor. The compressed air mixes with the liquid, causing the gasliquid mixture to be less dense than the rest of the liquid. Operation of a submerged hollow fiber membrane bioreactor. The platform is scalable from the lab bench to manufacturing.
Projects to generate grams of monoclonal antibody have been successfully managed with this system, for example, in cell. In this article, cell growth in a novel micro hollow fiberbioreactor was compared to that in a tflask and. Advantages o provides scale out capacity with significant advantages. Each bioreactor contains thousands of hollow fibers that simulate living capillary systems. Hollow fiber bioreactor systems increase cell culture yield. Hollow fiber membrane bioreactor for cod biodegradation of. A hollow fiber bioreactor from fibercell systems is the ideal method for the in vitro production of 25mg on up to gram quantities of a monoclonal antibody. Simple and effective oxygen supply the ohio state university low energy requirement uniform distribution of energy. In addition, the packing density was increased by 20% by optimizing. Advances in fiber construction and methods for oxygenation have the potential to bring the advantages of hollow fiber cell culture to biomanufacturing. Crosssection of hollow fibers in fibercell systems hollow fiber bioreactor. Its a timescalable production process thats ideal for generating significant amounts of very concentrated evsexosomes, mabs or recombinant proteins.
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