Hollow fibre cell culture

Continuous culture of up to 1e10 cells in a standard incubator

Hollow Fibre bioreactor modules

A compact FiberCell Systems Hollow Fibre bioreactor enables any lab to continuously culture large numbers of cells at high density inside a standard incubator.  Cell density 100 x higher than T-Flask is possible. This is a proven system for generating significant amounts of concentrated EVs/exosomes, mAbs  or recombinant proteins.

 

Cell-secreted products accumulate to high concentration

Hollow Fiber Bioreactor cartridge cross-section

Stylized schematic showing 3 fibres only

Porous fibres with a molecular weight cutoff retain cells and cell-secreted products. Repeated sampling or collections of very concentrated products can be made over many weeks, as required.

Lab Scale Hollow Fiber Cell Culture

FiberCell Systems Inc. (USA) established 2000.
Widely referenced in literature see publications lists.

Efficient scale up of cell culture

A single 20ml C2011 cartridge can continuously maintain >1E+9 cells and a single Duet pump can accommodate two independent cartridges (3.5ml, 20ml or 70ml). The system enables a time-scalable production process that’s ideal for generating large amounts of very concentrated Monoclonal Antibodies, fully and uniformly glycosylated Recombinant Proteins, or Extracellular Vesciles. The system can be 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 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 3-dimensional 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.

VIDEO – how does a hollow fibre bioreactor work?

Discover the technical points that make this method increasingly popular with researchers who want to efficiently produce cell-secreted products.

 

How to harvest from a FiberCell cartridge?

Harvesting is carried out in the laminar flow cabinet. The cartridge and media reservoir are in a closed loop which is easily decoupled from the Duet pump for transfer to the laminar flow cabinet. Using syringes, product-enriched supernatant can be periodically collected. 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 from a hollow fibre bioreactor.

Simple disposable cartridge module
A FiberCell® hollow fibre bioreactor 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.

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.

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

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