FiberCell Systems Lab-Scale Hollow Fibre Bioreactor

Hollow fiber bioreactor image

A hollow fibre bioreactor enables the continuous culture of large numbers of cells at high density.  It’s a time-scalable production process ideal for generating significant amounts of very concentrated EVs/exosomes, mAbs  or recombinant proteins. For example, up to gram amounts of monoclonal antibody can be produced with hybridomas.

Any cell culture laboratory with a standard size incubator can use a compact FiberCell Systems Hollow Fibre bioreactor. Many customer publications are available that refer to the use of this method.

Hollow Fiber Bioreactor cartridge cross-section

Stylized schematic showing 3 fibres only

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KDBIO is the European distributor for FiberCell Systems Inc.

Product harvesting

A hollow fibre cartridge contains a bundle of many hundreds of porous, protein-retentive hollow fibre filters made of polysulfone. The cell compartment around the fibres is perfused with media recirculated through the fibres thereby providing optimal conditions for continuous long-term culture. Cell densities can reach or exceed 1E+8 cells per ml. The fibre MWCO traps and concentrates secreted products in the cell compartment from which supernatant, that is highly enriched in target product, can be periodically collected.

Simple disposable cartridge module
A FiberCell® hollow fibre cartridge module is a simple-to-use consumable device with built-in gas exchange tubing. The cartridge is installed on a FiberCell Duet pump which is maintained on the shelf of an incubator. It is easy to unclip the cartridge with media reservoir from the pump and work with it in the laminar flow cabinet to harvest product with syringes. Up to 10^9 cells can be maintained in a 20ml Medium Size cartridge. A single harvest from this cartridge can be equivalent to 2 litres of flask culture media and several harvests can be collected per week, every week. Scaling up is straightforward and does not necessarily require more hardware.
Continuous culture at high cell density
Mimicking the flow of blood through capillaries, media is recirculated through the hollow fibres. A very large number of cells grow around the fibres in the extra-capillary space (ECS) of the cartridge to almost tissue-like density.  Nutrients, metabolites, drug compounds and gases etc., are very efficiently exchanged across the semi-permeable fibre walls. This is a much more in vivo like way to grow cells compared to static flask culture and is the basis for some intriguing recent research papers.

Hollow fibre bioreactor schematic

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Advantages of Hollow Fibre Culture

Efficient scale up of cell culture
A single 20ml C2011 cartridge can continuously maintain >1E+9 cells  and up to 1E+11 cells can be cultured using 2x 70ml cartridges on a single Duet pump. This enables a time-scalable production process that’s ideal for generating very concentrated monoclonal antibodies, fully glycosylated recombinant proteins, or EVs that can run for weeks or even months, as required, with little hands on time.
Highly concentrated secreted product
Secreted MAbs, recombinant proteins or exosomes accumulate in the bioreactor ECS to attain concentrations that can be 100X higher than flask or roller systems. To see the harvesting process watch this video
Biologically relevant culture conditions
Classical batch-style 2D cultures in flasks or low-density suspension culture in spinners or shakers do not provide an “in vivo like” culture environment. High density culture (>1-2 x 108 cells/ml) is possible in a FiberCell® hollow fibre bioreactor (HFBR). These conditions strongly favour, for example, the correct folding, assembly and post-translational modifications that are essential for the biological activity of secreted proteins. See our customer publications on 3D culture of cancer cells and  Production of “Difficult-to-Express Proteins”
Long term perfusion culture with no cell passaging
Perfused cells are continuously nourished and waste products are continuously removed while cell mass is automatically reduced during harvesting so cell passaging is not necessary. A FiberCell bioreactor cartridge module can be selected to culture from 1 to 50 billion cells in continuous high density exponential growth phase to give optimal productivity for long periods.

Cross-section of a hollow fiber bioreactor culturing lymphocytes in suspension.

Cartridge membrane area/volume is around 100-200cm2/ml enabling cells to remain viable at high density over weeks or months. The cyclic “feast-or-famine” conditions in classic systems is avoided and the metabolic status of the cultured cells optimized for high-efficiency bioproduction.

FiberCell® Hollow Fiber Bioreactor

No shear stress
Cells are located in the extra-capillary space (ECS), separated from the circulating medium by a semi-permeable membrane, and so are not exposed to shear stress.
Should your experiment require exposure of cells to shear stress, please enquire to discuss our special hollow fibre culture approach.

An inherently serum-free culture method
High cell densities permit a single-step switch to a universal protein-free serum replacement: CDM-HD. Low-serum or serum-free operation confers major advantages such as easier purification, lower costs, better more consistent yields and less risk of contamination from mycoplasma and viruses.
Suitable for suspension and anchorage-dependent cells
Most anchorage dependent cells readily attach to polysulfone hollow fibres. The total fibre surface area available for cell adhesion is very high, e.g. a medium size cartridge offers 3000 cm2 of area. A FiberCell bioreactor is also ideal for suspension cells but there is no requirement to spend time and effort developing cells especially for suspension culture.

Small footprint
A standard CO2 incubator can accommodate one FiberCell® HFBR per shelf. Larger incubators can house several units for simultaneous production of various different antibodies, for example.
Polysulfone vs cellulosic hollow fibre bioreactors
Polysulfone hollow fibre cartridges provide 10x more flow rate than cellulosic hollow fibre cartridges so have completely superseded the latter in recent years, apart for certain specific applications.
FiberCell® hollow fibre cartridges are available with different total surface areas of hollow-fibre membrane, volumes and oxygenation capacity. Free expert advice is available for set up and scale up.

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Special application : antimicrobial PK/PD
FiberCell® cartridges provide a unique approach for testing antimicrobial compounds. The system is increasingly used for in vitro PK/PD studies to de-risk novel lead compounds or combinations of existing antibiotics[more].
A better way to grow cells – PDF poster download :

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