How Does a Hollow Fibre Bioreactor Work?

A FiberCell® Systems hollow fibre bioreactor enables you to culture cells at much higher density than any other culture method. A FiberCell cartridge contains a bundle of many hundreds of hollow fibre filters made of polysulfone or cellulose. The fibres are around 200 µm diameter and are semi-permeable with a choice of molecular weight cutoff (MWCO), 5kd, 20kd, or pore size 0.1µm.

Stylized schematic showing 3 fibres only

A FiberCell® cartridge opened
at one end to show fibres

A better way to grow cells
Here is a useful infographic on hollow fibre technology and applications
Continuous perfusion
Mimicking the flow of blood through capillaries, media is recirculated through the hollow fibres. Cells grow around the fibres in the cartridge in the extra-capillary space (ECS) to ultra-high density (>1-2 x 108 cells/ml).  Nutrients, metabolites, drug compounds and gases etc., are very efficiently exchanged across the semi-permeable fibre membranes. Secreted products are retained by the fibre membranes in the ECS where they accumulate to high concentration for convenient periodic harvesting.

Hollow fibre bioreactor schematic

Oxygenation and waste removal
A pulsatile perfusion pump draws medium from the reservoir bottle and pushes it through the cartridge module oxygenation circuit (silicone tubing coil) where it is oxygenated and saturated with CO2 prior to flowing through the cartridge. Waste products diffuse away and are diluted in the circulating medium.

Advantages of Hollow Fibre Culture

Long term perfusion culture with no cell passaging
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.

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

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 Systems bioreactor enables you to maintain from 1 to 50 billion cells at high density in continuous exponential growth phase to give optimal productivity for long periods.
Biologically relevant culture conditions
Classical batch-style 2D cultures in flasks or low-density suspension culture in spinners or shakers are not biologically relevant systems. High density cultures that closely approximate the in vivo cellular environment (>1-2 x 108 cells/ml) are possible in a FiberCell® hollow fibre bioreactor (HFBR).

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.
Serum-free operation
High cell densities facilitate adaption 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.
High protein concentrations
Secreted MAbs and recombinant proteins accumulate in the bioreactor ECS to attain concentrations 100X higher than with classic culture systems. FiberCell® cartridges enable cells or proteins to be easily sampled or harvested periodically from the extra-capillary space in a 15 minute operation, see video.
Suitable for suspension and anchorage-dependent cells
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.
Special application : antimicrobial PK/PD
FiberCell® cartridges provide a unique two-compartment system that is widely used to mimic the in vivo intravascular and extravascular compartments. The system is increasingly used for in vitro PK/PD studies of antibiotics or anti-viral compounds, for example [more].
Small footprint
A standard CO2 incubator can accommodate more than one FiberCell® HFBR.
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.
Scalability
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.
The advantages of HFBR
technology are
comprehensively summarized
in this article
Applications for Hollow Fibre Technology
Applications for HFBR systems also include:
  • Expansion of peripheral blood lymphocytes, CD4+, CD8+ PBL subsets and bone marrow stem cells
  • Continuous collection of stem cells (co-culture of cells from human placenta perfusion)
  • Co-cultivation of two cell lines (usually consisting of the feeder cells and the expansion cell line)
  • Liver model
  • Gut model