What is Tangential Flow Filtration?

biotechnology fundamentals Aug 26, 2023

Tangential Flow Filtration (TFF), also known as Crossflow Filtration, is a widely used separation technique in biologics manufacturing for processes such as concentration, diafiltration, and buffer exchange of biomolecules. It's particularly effective for large-scale purification and concentration of biologics products such as antibodies.

How Tangential Flow Filtration (TFF) Works

TFF operates on the principle of convective mass transfer. Unlike traditional dead-end filtration, where the liquid is pushed through the filter, TFF involves the continuous circulation of the feed solution tangentially across the surface of a semi-permeable membrane. This creates a flow that prevents the accumulation of retained material on the membrane surface.

The video below is a great tool to visualize tangential flow and demonstrates the key components of a TFF system and common checks, samples and data collected during operation:


Key System Components:

The key components of the TFF system are typically assembled in a recirculating loop:

  • Feed Solution:
    This is the solution containing the biomolecules that need to be processed, such as a protein solution from cell culture.

  • Semi-Permeable Membrane:
    The membrane is the heart of the TFF system. It allows the solvent and smaller molecules to pass through, while retaining larger molecules like proteins.

  • Pump:
    A pump is used to create the necessary flow of the feed solution along the membrane.

  • Pressure Monitor:
    It helps regulate the pressure in the system, especially the differential pressure across the TFF membrane.  In production scale biologics manufacturing, damage of the membrane by excessive pressure typically requires a deviation investigation as it will likely result in failure at a significant or critical step.

  • Retentate:
    The concentrated solution that does not pass through the membrane.

  • Permeate:
    The filtered solution that passes through the membrane.

One of the most important points in TFF process design, operation and training is ensuring clarity with the operations team on the size of the target molecule with respect to the size of the membrane.  This relationship will determine if the target molecule is being retained in the loop (retentate) or filtered through the membrane (permeate). 

TFF Applications in Biologics Manufacturing:

TFF systems are very commonly used in harvest and formulation steps because of their ability to concentrate, dilute, exchange buffers and purify by size.

  • Concentration:
    TFF can be used to concentrate dilute biomolecule or cellular solutions.
  • Diafiltration:
    This process helps replace the original buffer or solvent with a new buffer or solvent, important for adjusting pH, salt concentration, or other solution properties.
  • Buffer Exchange:
    Similar to diafiltration, buffer exchange is used to change the solution environment of the biomolecules or cells.
  • Ultrafiltration:
    Ultrafiltration is purification based upon molecule size.  Smaller molecules and solvent are passed through the membrane while retaining larger molecules. For example, TFF can be used to remove viruses from a solution, as viruses are typically larger than the biomolecules of interest.

This post is a part of our 'Biotechnology Fundamentals' blog series, crafted especially for those stepping into the world of biopharmaceutical manufacturing. Weather you are an entry level employee or changing industry into large scale biologics or cell therapy, this series will help you orient to the basic manufacturing and quality concepts.  

 Follow along to build a strong foundation, gain clarity, and learn more about the rapidly growing world of biotech.