Hollow fibre bioreactor

FiberCell Systems Laboratory-Scale Hollow Fibre Bioreactor (fits on shelf of incubator)

Hollow fiber bioreactor image

A FiberCell Systems Hollow Fibre bioreactor enables the continuous culture of large numbers of cells at high density.  It’s a time-scalable production process that’s ideal for generating significant amounts of very concentrated EVs/exosomes, mAbs  or recombinant proteins. Projects to generate grams of monoclonal antibody have been successfully managed with this system, for example, in cell culture laboratories furnished with standard facilities.

Continuous culture at high cell density
Hollow Fiber Bioreactor cartridge cross-section

Stylized schematic showing 3 fibres only

Animation showing how a hollow fibre bioreactor works.

N.B. cartridge and reservoir can be unclipped from the pump as a sterile-sealed unit which makes the FiberCell System very practical for laboratory use.

Product harvesting

The cartridge and media reservoir form a closed loop that can easily be decoupled from the Duet pump and transferred to a laminar flow cabinet for harvesting and media changes. Using syringes, product-enriched supernatant can be periodically collected from the cell compartment. The molecular weight cut-off of the hollow fibres traps and concentrates secreted products to give very high yields. Up to 100X greater product concentration than with flask culture is routinely possible.

Download FREE e-Book: “Advantage of Hollow Fiber Bioreactors”
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.

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 large amounts of very concentrated monoclonal antibodies, fully glycosylated recombinant proteins, or EVs. The system can be run for weeks or even months, as required, with little hands on time.
Fits on the shelf of an incubator
Any cell culture lab with a standard incubator can use the FiberCell Hollow Fibre Bioreactor. The compact DUET Pump fitted with 2x independent hollow fibre cartridges and 2x media bottles will require just one shelf and no special connections. See: Duet Pump.
Highly concentrated secreted product
Secreted mAbs, recombinant proteins or exosomes accumulate in the cell compartment to give yields per millilitre up to 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.
In vitro models – See our customer publications on 3D culture of cancer cells , “3D-exos” and  Production of “Difficult-to-Express Proteins” 
No shear stress on cells
Cells grow around the fibres and so are not in contact with the media flow and this means they are not subjected to shear stress. These conditions prevent the build up of contamination from cell debris. Even the least viable cells appear to remain intact in this system which is ideal for simplifying downstream purification processes.
Optimal for high fidelity protein expression
Accumulating evidence points to the fact that the more in-vivo like 3D-culture conditions in the FiberCell bioreactor promote the correct folding, assembly and post-translational modification of recombinant proteins.
Avoids passaging
Cells can comfortably grow post-confluently in three dimensions in a hollow fibre bioreactor. Passaging is not required. Periodic harvesting of supernatant will also remove cells and this controls the cell mass in the system.
Reduces plasticware trash
A lot of T-flasks are needed to grow 10^9 cells whereas with the FiberCell System this number of cells can be continuously maintain in a single 20ml hollow fibre cartridge.
Uses an economical chemically-defined media formulation
Users of this high density culture method can exploit the natural ability of cells to effectively condition their environment with growth and differentiation factors. This means serum can be replaced by a simplified and economical chemically defined formulation (FiberCell Systems CDM-HD Chemically Defined Serum Replacement).
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.

Further scale-up is easy
It’s easy to scale up from a basic starter system. FiberCell Systems hollow fibre cartridges are available with different fibre areas, cartridge volumes and oxygenation capacity.

Polysulfone vs cellulosic hollow fibre bioreactors
Polysulfone hollow fibre cartridges provide much higher flux rate than cellulosic hollow fibre cartridges so have completely superseded the latter in recent years, apart for certain specific applications.

Visit our application pages

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 – single page PDF download

Request a FREE flashdrive with instructional videos : info@kdbio.com