Hollow fibre cell culture : compact, efficient, productive

Hollow Fiber Bioreactor cartridge cross-section

Stylized schematic showing 3 fibres only

Hollow Fibre bioreactor modules

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

A hollow fibre bioreactor (HFBR) provides a huge surface area for cell attachment in a low volume cartridge. The porous semi-permeable fibre walls have a molecular weight cutoff to retain both cells and cell-secreted products.

Cells are typically inoculated into the space around the fibres. Media recirculating on the luminal side not only provides the cells with nutrients and oxygen but simultaneously removes waste metabolites resulting in stable high density culture: cell numbers can reach as high as 2 billion in a scaleable 20ml bioreactor.

Repeated collections of concentrated cell-secreted products 

Multiple harvests of supernatant enriched in target product can be taken over many weeks. This is a proven system for generating significant amounts of concentrated EVs/exosomes, mAbs or recombinant proteins.

Using this approach any R&D lab can consider generating up to industrial scale quantities of their target product.

Efficient scale up of cell culture

Maintain >1E+9 cells in 20ml HFBR cartridge. A single Duet pump accommodates two independent cartridges (3.5ml, 20ml or 70ml). The FiberCell system provides a time-scalable production process ideal for generating large amounts of very concentrated Monoclonal Antibodies, Extracellular Vesicles (exosomes), or fully and uniformly glycosylated Recombinant Proteins.

Highly concentrated secreted product

Secreted mAbs, recombinant proteins or exosomes accumulate in the cell compartment to give yields per ml up to 100X higher than flask or roller systems. 

Avoids passaging cells

Passaging is not required because cells grow post-confluently in three dimensions in an HFBR. Maintaining a 20ml cartridge (harvesting and media changeg) takes just 15 minutes per weekday. Harvesting of supernatant will also remove cells and this controls the cell mass in the system.

Biologically relevant 3-dimensional culture conditions

A FiberCell HFBR provides an artificial capillary bed for growing cells long-term at high density. Our photo gallery shows examples of how different cell types can appear – Photo Gallery. Several customer publications refer to HFBR culture as a more in-vivo like culture method: 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 are not in contact with the media flow which means they are not subjected to shear stress. These gentle conditions prevent contamination from cell debris. Even the least viable cells will remain intact in this system. 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.

Reduces plasticware trash

A huge number of T-flasks would be needed to grow 10^9 cells whereas with the FiberCell System even more cells than this can be maintained continuously on a single shelf of a standard incubator.

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 4000 cm2 of area. Suspension cells such as THP1 also grow fine in this system however there is no point spending time and effort to develop cells specifically for suspension culture if you plan to use a FiberCell bioreactor.

How to harvest from a FiberCell cartridge?

Harvesting is carried out in the laminar flow cabinet (it is very easy to unclip the cartridge with its media reservoir from the Duet pump which stays in the incubator at all times). 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.

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 fits on the shelf of an incubator. 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 and relatively inexpensive to scale up / out from the basic starter system. FiberCell Systems hollow fibre cartridges are available with different fibre surface areas, cartridge volumes and oxygenation capacity. All the cartridges work on the same Duet pump.

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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