What is Tangential Flow Filtration?
Tangential Flow Filtration (TFF) Basics for Biologics Manufacturing
Tangential Flow Filtration (TFF), or Crossflow Filtration, is a core separation method used in biopharmaceutical manufacturing. It’s essential for concentrating, diafiltering, and buffer exchanging biomolecules—especially proteins like antibodies.
How TFF Works
Unlike dead-end filtration, TFF circulates liquid tangentially across a semi-permeable membrane. This crossflow prevents buildup on the membrane surface, improving efficiency and filter longevity.
A good visual reference:
This video provides an overview of tangential flow filtration or TFF.
Key TFF System Components
- Feed Solution: Contains biomolecules such as proteins from cell culture.
- Semi-Permeable Membrane: Retains large molecules; lets smaller ones pass.
- Pump: Maintains recirculating flow across the membrane.
- Pressure Monitors: Essential for tracking differential pressure. Excess pressure can damage membranes, triggering deviation investigations in GMP environments.
- Retentate: The concentrated solution that stays in the loop.
- Permeate: The filtered solution passing through the membrane.
Critical Note: The size relationship between the target molecule and membrane pore size determines what gets retained or filtered. This is a key point in operator training and process control.
Common TFF Applications in Biologics Manufacturing
- Concentration: Increasing the concentration of biomolecules from dilute solutions.
- Diafiltration: Replacing one buffer with another—critical for adjusting pH, salt concentration, or solvent conditions.
- Buffer Exchange: Similar to diafiltration but typically with tighter process requirements.
Ultrafiltration: Size-based purification. For example, TFF can retain larger virus particles while allowing smaller proteins to pass.
This article is part of our Biotech Basics series—designed for those entering biopharmaceutical manufacturing, whether you're new to the industry or shifting from a different role.
Follow along to build foundational knowledge, clarify manufacturing and quality concepts, and get oriented to the growing world of biologics and cell therapy.
