Protein Production Scale Up in Hollow Fiber Bioreactor Systems

For many years, hollow fiber cell culture has been a unique platform that has many benefits including utilization of a closed system, single-use products, and 3D cell culture. Proteins can be difficult to express, especially those that are highly complex or glycosylated. Because of this, traditional cell culture methods can make protein production challenging, hence the need to use hollow fiber bioreactors. Here are details on how hollow fiber bioreactors increase protein production in cells.

How are Hollow Fiber Bioreactor Systems Different from Other Methods?

Four main characteristics distinguish hollow fiber cell culture from other methods:

  • Cells do not use a plastic dish, microcarrier bead, or impermeable support for perfusing and bounding. Instead, they use a porous matrix giving an in vivo-like environment.
  • Molecular weight cut-off (MWCO) is controllable.
  • Surface-area-to-volume ratio is high, resulting in higher cell densities.
  • Serum requirements for cell culture are greatly reduced.

How do Hollow Fiber Bioreactors Increase Protein Production

Hollow fiber bioreactors have thousands of semipermeable capillary membranes known as hollow fibers. These fibers are closely packed in a cylindrical cartridge with an inlet and outlet on each end. The tight packing of the fibers allows for the seeding and high-density growth of cells in the extra capillary space (ECS).

The cell culture media continuously flows within the fibers’ intracapillary space (ICS). With the help of the molecular weight cut off of the hollow fiber, you can control molecular flows. Therefore, small molecule nutrients and oxygen can flow through the fibers to the cells. The waste will move across the fibers to the intracapillary space, where it flows out.

In addition, the MWCO retains the larger molecular weight products like monoclonal antibodies, viruses, recombinant proteins, and cells inside the extra capillary space. The used media can be recirculated or removed from the system. The inflow and outflow of nutrients and waste from the cells within the 3D culture configurations creates an in vivo-like environment which is ideal for cell growth in high densities.

Advantages of Hollow Fiber Bioreactors

  • Daily maintenance requires little time and does not require splitting of cells
  • Cell cultures are maintainable for many months of ongoing production.
  • Cell culture conditions improve protein assembly and folding.
  • Small volumes can be harvested at a higher concentration for easy handling and efficient processing.
  • Fewer cells are needed for seeding since no seed reactor is used.
  • Minimal needs for cell lysis, less DNA contamination, and host cell protein.

A hollow fiber bioreactor system presents laboratories with opportunities to utilize the glycosylation and superior environment for folding that is provided by expression in mammalian cells. In addition, this method effectively produces concentrated products with reduced protein, DNA, RNA, and protease contamination.