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TFF: The Technology

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Tangential Flow Filtration (TFF), also called Cross Flow Filtration (CFF), is a rapid and efficient method for filtration and separation of solutions containing biomolecules, or particles such as viruses, bacteria or cellular material. It is a process whereby product flow (feed) is directed tangentially along the surface of a membrane with most of the solution circulated back to the feed tank.

The rapid flow of feed solution across the membrane acts to ‘sweep’ the surface, reducing concentration polarization (product concentration at the membrane surface). It also prevents build-up of foulants that can plug the pores at the membrane surface. The rapid cross flow creates a pressure drop, which forces some of the feed solution and dissolved molecules that are smaller than the pores in the membrane, through the membrane filter. The solution that passes through the membrane is referred to as filtrate or permeate. Molecules or particles larger than the membrane pores are retained in the feed solution and effectively concentrated.

Membrane filtration can be classified as either a microfiltration (MF) or ultrafiltration (UF) process. Microfiltration membranes, with pore sizes typically between 0.1 micron and 1 micron, are generally used for clarification, sterilization and removal of micro-particulates or for cell harvesting. Ultrafiltration membranes, with much smaller pore sizes between 0.001 and 0.1 micron, are used for concentrating and desalting dissolved molecules (protein, peptides, nucleic acids, carbohydrates and other biomolecules), exchanging buffers, fractionation and water purification. Ultrafiltration membranes are typically classified by Molecular Weight Cut Off (MWCO), rather than pore size.

The fluid dynamics of cross flow filtration reduces membrane fouling and maintains filtration rates (flux) for a longer period of use, thus increasing membrane throughput (greater capacity) compared to traditional cartridge (direct flow) filtration. Additional advantages of TFF include the ability to reuse the filter modules and relatively low capital costs.

TFF can be applied to a wide range of biological fields. It is applicable to R&D discovery applications right through pilot and full-scale production. TFF can be used to concentrate and desalt sample solutions ranging in volume from a few milliliters to thousands of liters. It can be used to fractionate large from small biomolecules, harvest cell suspensions and clarify fermentation broths and cell lysate.

TFF Applications

Microfiltration and ultrafiltration processes incorporating tangential flow or cross flow filtration is utilized in a wide range of biopharmaceutical applications. Examples of a few typical applications are listed below:

  1. Concentration and desalting of protein, peptide, and oligonucleotide solutions
  2. Purification and recovery of antibodies or recombinant proteins
  3. Vaccine and conjugate concentration and diafiltration.
  4. Fractionation of protein mixtures
  5. Blood plasma fractionation and purification
  6. Cell broth clarification, concentration
  7. Cell culture perfusion such as in monoclonal antibody (Mab) production
  8. Clarification of Fermentation broths
  9. Concentration and washing of bacterial cells
  10. Water and buffer purification (endotoxin removal)

Ultrafiltration Applications

Omega™ polyethersulfone (PES) and Delta regenerated cellulose membrane cassettes and their associated hardware and systems are the first choice in applications that require precise tailoring of membrane characteristics and gentle processing. Membrane cassettes are the preferred technology for concentration and diafiltration applications for recombinant proteins and other biological process fluids.

Microza hollow fibers offer advantages for endotoxin removal from buffer preparation and pharmaceutical water applications.

Microfiltration Applications

PallSep™ Biotech systems provide gentle, efficient separation in complex biotech harvest and clarification applications such as the concentration, clarification, and purification of high particle load, high viscosity or difficult-to-filter solutions such as fermentation broths or lysates.

Microza* hollow fiber modules are the preferred choice for clarification of fermentation broths and cell culture fluids. They are often used for concentration, washing and recovery of bacterial cells prior to lysing and recovery of inclusion bodies and recombinant proteins from the cells. Reliability, mechanical strength, simple flow geometry and steam sterilizability make Microza hollow fiber modules an excellent option for perfusion cell culture.

Supor® TFF suspended screen channel membrane cassettes can be used in batch applications for the harvesting of bacterial, mammalian or insect cells. They may also be used for lysate clarification.

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