How Do They Work?

Hollow Fiber Bioreactors are used globally for GMP- and ISO-regulated products

Features

Single-Use

  • Supplied sterile and ready to use
  • No cleaning validation expense
  • Easy set-up and take-down

Continuous Production

  • Continuous harvest protects product quality
  • Continuous media perfusion:
    • Promotes tissue-like cell density
    • Extends run length for flexible production

Automated

  • Decreases labor
  • 30 minutes to start run
  • 10 hours of labor per month to maintain
Electron Micrograph image of the hollow fiber capillaries in cross-section with a cell mass growing on the cell side.

Electron Micrograph image of the hollow fiber capillaries in cross-section with a cell mass growing on the cell side.

Circuit diagram of a hollow fiber cartridge showing the two compartments of a hollow fiber and their flow paths: Cell Side (EC) and Media Side (IC).

Circuit diagram of a hollow fiber cartridge showing the two compartments of a hollow fiber and their flow paths: Cell Side (EC) and Media Side (IC).

How it works: A closer look

A simplified cross-section of a hollow fiber cell culture cartridge depicting one hollow fiber (red circle) inside the clear casing (blue circle).

A simplified cross-section of a hollow fiber cell culture cartridge depicting one hollow fiber (red circle) inside the clear casing (blue circle).

How it works: The circuits

  • The cell culture cartridge was designed to maintain long-term viability and tissue-like density of mammalian cells (see image above)
  • Hollow fibers are semi-permeable capillary tubes made of polymers approximately 200µm in diameter
  • The semi-permeable walls of the hollow fibers allow the exchange of oxygen, nutrients, and waste (see below) without diluting expressed protein products
  • The hollow fibers create a high surface area to volume ratio for high density culture (e.g. 2.1m2 cartridge has a 155 mL volume)
  • The hollow fiber separates two media circuits:
    • The “cell side” outside the hollow fibers (extracapillary/EC space)
      • Cells grow to tissue-like density
      • Product is retained by the hollow fiber membrane
      • Growth supplement-enriched media perfuses at a very slow rate
      • Concentrated product can be harvested continuously or in batches
    • The “media side” inside the hollow fibers (intracapillary/IC space)
      • Media Exchange: nutrient delivery and waste products are controlled by the addition of fresh media and removal of spent (product-free) media
      • Media Circulation: media passes continuously through a non-sparging gas exchange cartridge (oxygenator) to deliver oxygen and control pH
      • Media circulation speed and rate of media exchange are independently controlled to provide options for process optimization
      • Hollow fiber membrane eliminates shear stress
  • EC Cycling:
    • What it is:
      • Automated, bi-directional active mass transfer of nutrients and waste across the semi-permeable walls of the hollow fiber membrane
      • Occurs uniformly throughout the cell culture cartridge
    • What it does:
      • Ensures even distribution of oxygen and nutrients throughout the cartridge
      • Eliminates microenvironments and gradients in the cell mass
  • Continuous perfusion and harvesting:
    • Supports long runs (>60 days)
    • Decreases the risk of protein degradation