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Tangential flow filtration (TFF), sometimes called cross-flow filtration, is a separation technique commonly used in biopharmaceutical applications and life science research. This filtration technique derives its name from the tangential feed flow across a surface filter. Use tangential flow filtration for feeds that contain high proportions of solids with small particle sizes where the permeate is the molecule of interest. This is because solid materials can speedily clog the filter surfaces during normal flow filtration.

The primary applications for TFF are concentration, diafiltration (desalting and buffer exchange), and fractionation of large from small biomolecules. You can also use TFF for to clarify and remove cells or cellular debris from cell culture or fermentation media.

Advantages of TFF

Reasons to choose TFF instead of normal flow filtration (NFF) include:

  • TFF prevents “filter cake” formation, for high liquid removal rates.
  • Process feed stays as a mobile slurry that’s usable for further recirculation.
  • The solid content of the product slurry is highly variable.
  • You can fractionate particles by size during TFF.
  • Applications of TFF

    • Protein purification
    • Decontamination of feeds
    • Diafiltration (DF) for buffer exchange
    • Desalination and concentration of biomolecules like proteins and DNA or RNA
    • Harvesting mammalian cell lines, bacteria, or yeast
    • Whole cell lysate clarification and desalting
    • Chromatography sample preparation

    Tangential flow filtration FAQs

    Here are answers to some frequently asked questions about tangential flow filtration.

    What is tangential flow filtration (TFF)?
    TFF is a separation technique where a feed is passed across a filter membrane at positive pressure relative to the permeate side to remove impurities. Components that are smaller than the tangential flow filter pore sizes are retained on the feed side of the membrane as retentate.

    Why use TFF?
    During TFF, the bulk of fluid across the membrane easily clears off trapped particles on the surfaces, allowing continuous operation of filters and high solid loads without excessive clogging.

    How do you optimize tangential flow filtration?
    Optimize TFF processes by controlling key parameters such as cross flow rate, transmembrane pressure, and type of filter membrane. Cleaning-in-place (CIP) is a technique to clean the filters of systems used heavily. Single-use hollow fiber cartridges are another option, and these remove the need for cleaning protocols and cleaning validation.

    What's the difference between ultrafiltration (UF) and diafiltration (DF)?
    Commonly used in buffer exchange, diafiltration offers increased storage stability and ease of administration, while ultrafiltration membranes help to concentrate the sample to its final formulation concentration.

    What products does Cytiva offer for tangential flow filtration?
    We offer single-use and conventional hollow fiber filters and TFF systems suitable for a range of uses, from lab scale up to manufacturing. Our automated ÄKTA™ TFF systems use UNICORN™ software common to our chromatography systems, making them well-suited as part of a larger protein purification workflow.