Hollow fiber membrane life in membrane bioreactors mbr. Adhesion and differentiation of endothelial cells by exposure to chronic. Brisbane and womens hospital human research ethcells are loaded into the fiber lumens from the syringe head. Setting up a fibercell systems hollow fiber bioreactor.
Also disclosed is a novel harvest media for use in directly reseeding adherent cells into a hollow fiber bioreactor. Hollow fibre membrane bioreactors hfb provide a novel approach towards tissue engineering applications in the field of regenerative medicine. Corresponding factors also exist for the zeeweed hollow fiber membrane points 4 and 5 below, but the list was expanded as follows for the purpose of the discussion in this paper. Us10577582b2 method of reseeding adherent cells grown in. Optimizing t cell expansion in a hollowfiber bioreactor. The system conveniently fits inside a standard co2 incubator. Hollow fiber was the dominant product segment and accounted for 80. Hollow fiber bioreactors for in vivolike mammalian tissue. A novel anaerobic electrochemical membrane bioreactor. Ethanol production saccharomyces cerevisiae immobilized. 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. The product is expected to witness significant growth on account of its low maintenance and operational cost as compared to multitubular and flat sheet.
An improvement in small scale hollow fiber bioreactor systems is described. Hollow fiber bioreactors, for example, feature a fibrous membrane structure 50. 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. Ideal for ultrafiltration, diafiltration and microfiltration, singleuse hollow fiber filters for tangential flow filtration are packed in housings engineered to handle high pressures, with a choice of fiber chemistries and sizes from process development to manufacturing. Cell and medium preparation umbilical cord blood from fullterm deliveries was figure 1. However, the antibody productivity of the batch harvest system fell off rapidly after day 20 resulting in only 4. This manuscript describes in detail the setup and operation of a hollow fiber bioreactor system for the in vivolike culture of mammalian cells. The experiments were carried out in petris dishes and in. Libicki and channing r, a theoretical investigation of convective transport in the hollowfiber reactor, chemical engineering.
Cell and medium compartments of the bioreactor are separated by a semipermeable membrane, and oxygenation of the cell compartment is accomplished using an oxygenation membrane. Fibercell systems hollow fibre bioreactor for high density. Liver tissue was simply digested with collagenase, and this mixture of cells was seeded into the hollow fiber bioreactor. Hollow fiber bioreactor technology for tissue engineering. I chose a hollow fiber bioreactor with a low molecular weight cutoff mwco, 5kda because i was interested in collecting 100% of a larger, secreted mutant protein 35 kda in the ecs. The closed environment of the bioreactor remains intact during the cell culture process, eliminating open events and handson. Pdf hollow fibre membrane bioreactors for tissue engineering. Typical automated hollowfiber perfusion bioreactor hfpb in. 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 is integrated into a compact platform that supports one or two independent fibercell cartridge modules with associated media reservoirs. Pioneered hollow fiber bioreactor platform spunoff as cell culture company january 2016 33,000 sq.
Application of submerged hollow fiber membrane in membrane bioreactors. Effect of harvesting protocol on performance of a hollow. Hollow fiber bioreactor technology william whitford, john w. A fibercell systems hollow fibre bioreactor enables the continuous culture of large numbers of cells at high density. A bioreactor equipped with hollow fiber microfiltration membranes was applied for wastewater treatment. The quantum system is comprised of a computer interface and a tubing adapter panel containing peristaltic pumps, fluid sensors. 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.
Complete indigenous technology to spin hemodialysis grade hollow fiber membranes by. A pump circulates ic medium from the ic reservoir, through a gas exchange cartridge, through the ics inside the bioreactor, and back to the ic reservoir. Kdbio distributor for the fibercell systems hollow fiber. I first primed the hollow fiber bioreactor cartridge and confirmed the sterility with pbs for a minimum of 24 hours prior to preculturing the system with 2 l of. 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. Cells were allowed to attach for 24 hours before transfection by an attach cells task. A obtained with informed consent, from both the royal bundle of hollow fibers is contained in a standard t75 flask. A hollowfiber bioreactor for expanding hiv1 in human. Since there are a wide variety of different bioreactors being used for mammalian cell culture, this document will not address specific bioreactor models.
This system can replace manual cell culture and produce cells that retain their phenotypes and functionality. Pdf modelling of hollow fiber membrane bioreactor for. Hollow fiber bioreactor configurations several hfb configurations have been proposed for organ and tissue engineering. The potential application of hollow fiber bioreactors to. This invention is directed to methods of directly reseeding harvested adherent cells grown in a hollow fiber bioreactor. Cadwell interest in exosomes has grown of late, particularly since they have been seen to take part in functional interactions with antigenpresenting cells, and in the modulation of the immune response in vivo. The hollow fiber bioreactor and cell cocultivation. The hollowfiber membrane systems have been used as bioreactors years ago due to the advantages that present, such as. Hollow fiber bioreactors comparison to stirred tank introduction cells are typically cultured in the ecs due to better cell retention. Hollow fibers with 10 kda molecular weight cutoffs are housed within a piece of silicone tubing. The hfbr system is a highdensity, continuousperfusion culture system. Hollow fiber bioreactors are the focus of scientific research aiming to mimic physiological vascular networks and engineer organs and tissues in vitro.
Filtration principles, operation, and membrane fouling ultrafiltration hollow fiber membrane bioreactor mbr treating oil refinery wastewater hollow fiber membrane contactors hollow fiber. A hollow fiber bioreactor is a 3 dimensional cell culturing system based on hollow fibers, which. Pdf human lymphocyte hollow fiber bioreactor sabrina. Demonstrating the first steps in setting up a hollow fiber bioreactor for preculture. Removal of chemical oxygen demand cod and biochemical oxygen demand bod 5 was investigated. 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. At the heart of every fibercell hollow fiber bioreactor system is the duet pulsatile pump. Dale, optimum fiber spacing in a hollow fiber bioreactor, biotechnology and bioengineering, 32, 8, 983992, 2004. In many ways, the hollow fiber bioreactor may be considered the original modern 3 dimensional cell. In this study, we modified a polytetrafluoroethylene ptfe hollowfiber membrane element used for submerged membrane bioreactors mbrs to reduce the energy consumption during mbr processes. Application of submerged hollow fiber membrane in membrane. The hollow fiber membrane bioreactor hfmb has been investigated for the cultivation of mammalian chinese hamster ovary cell expansion. Instead, it will focus on suggestions that should be applicable to a. Oxygenation in such systems is improved by the inclusion of a hollow fiber oxygenator oxy1.
The 3d environment created within a hollow fiber bioreactor is unique and effective at supporting stromasuspension cocultures in sufficient numbers over long periods of time, and has been shown to be potentially clinically useful. Hollow fiber membranes are ubiquitously used in industrial separations, especially the filtration of drinking water. Fundamental research of factors affecting cell growth in hollow. The terumo quantum cell expansion system is a hollow fiber bioreactor designed to expand cells to the 109 range in a manageable and compact culture vessel. Hollow fibre membrane bioreactors for tissue engineering. Largescale production of lentiviral vector in a closed. In these dynamic culture platforms, a hollow, porous fiber membrane with diverse filtration rates, fabricated from. The hollow fiber bioreactor for the reasons outlined above, there is currently tremendous interest in 3dimensional cell culture systems. A methodology for simplifying the solution procedure for hollow fiber bioreactor design equations has been described.
Pdf optimizing t cell expansion in a hollowfiber bioreactor. Small scale bioreactor systems provide a hollow fiber surface area of from 0. Pdf hollow fiber bioreactors are the focus of scientific research aiming to mimic physiological vascular networks and engineer organs and tissues in. The solution of hollowfiber bioreactor design equations american. A new anaerobic treatment system that combined a microbial electrolysis cell mec with membrane filtration using electrically conductive, porous, nickelbased hollowfiber membranes nihfms was developed to treat low organic strength solution and recover energy in the form of biogas. Harvest large quantities of secreted protein with hollow.
The reason for this lies in the interesting features of this bioreactor type, including excellent mass transport properties. The hollowfiber bioreactor provides a defined and stable geometry, which allows for the control and management of the cell culture environment. In order to more closely approximate in vivo cell growth conditions, richard knazek developed the hollow fiber bioreactor hfbr in 1972 1. These hollow fiber membranes are often bundled and housed within tubular polycarbonate shells to create hollow fiber bioreactor cartridges. This new system is called an anaerobic electrochemical membrane bioreactor anembr. Projects to generate grams of monoclonal antibody have been successfully managed with this system, for example, in cell. These reactors offer a very gentle means for immobilizing. Conversion of bioreactors to continuous perfusion using. Pdf municipal wastewater treatment using a hollow fiber. The hollow fiber bioreactor and cell co cultivation. Its a timescalable production process thats ideal for generating significant amounts of very concentrated evsexosomes, mabs or recombinant proteins. Pdf hollow fiber bioreactor technology for tissue engineering.
Hollow fiber membrane modules have been used as bioreactors to pro duce or transform chemicals. Pdf hollow fibre membrane bioreactors hfb provide a novel approach towards tissue engineering applications in the field of regenerative. Expansion and cellular characterization of primary human. Energy reduction of a submerged membrane bioreactor using. Hollow fiber bioreactor technology for tissue engineering applications article pdf available in the international journal of artificial organs 391 february 2016 with 702 reads. Despite the presence of starling flow as the dominant ec convection mechanism in the batch harvest system, the bioreactor start up was fairly good. 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.
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