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Tangential flow filtration (TFF), also called crossflow filtration, is a common technique used in biopharmaceutical manufacturing and in life science research to clarify or concentrate cell or microbial cultures. In a tangential filtration system, a feed, or starting mixture, is passed along a filter membrane surface rather than through it perpendicularly. TFF is a flexible process that allows for microfiltration or ultrafiltration. A difference in pressure across the filter drives molecules that are smaller than the pore size through the filter, while the feed solution continues to circulate. During tangential flow filtration, larger components are retained and pass along the membrane surface, before they flow back to the feed reservoir. Feed refers to the solution that gets directed to the membrane surface. The part of the liquid that passes along the filter membrane is the retentate, while the solution that passes through the membrane is the permeate.

In tangential filtration systems, the fluid flow along the membrane surface sweeps away the buildup of material on the filter surface to prevent filter clogging. Also, you can recirculate retentate solutions to allow thorough processing of large sample volumes for optimized purification.

Difference between TFF and normal flow filtration

There are three key differences between tangential flow filtration and normal flow filtration (NFF).

  • TFF filters use membranes to separate components in a feed stream, while NFF processes use membranes, paper, or other materials like glass fiber.
  • Automated tangential filtration systems allow the recirculation of retentate solutions, while feed passes through a filter only once in NFF.
  • In TFF systems, the retentate stays in solution to allow recovery. However, NFF requires you to resuspend materials collected on the filter for further processing.

Applications of tangential filtration systems

TFF is widely used in research, product development, and production of biopharmaceuticals for:

  • Cell harvesting
  • Clarification of cells or lysates
  • Fractionation of products
  • Product concentration
  • Diafiltration

Tangential filtration systems

Tangential filtration systems often comprise the following components:

  • Pumps and valves: One or more pumps control the liquid flow in the filtration system. Feed pumps help maintain the flow of feed into the filter, while retentate pumps control retentate flow. Many TFF systems use a permeate pump to manage the flow of permeate from the filter. Some feature transfer pumps that help add buffers to the feed reservoir at controlled rates. Valves with flow restrictors help to regulate flow in the different process lines. Controlled pump rates and valve restriction generate pressure across the membrane.
  • Pressure sensors: Sensors in the feed and retentate lines help monitor the process for maximum productivity.
  • Flow sensors: Placed at strategic points, flow sensors monitor the flow rates for feed solutions, permeates, and retentates.
  • Reservoir level sensors: These help the volume of liquid in the feed reservoir.
  • Air sensors: Located in the feed stream, air sensors facilitate the continuous monitoring of air bubbles in feed to limit the entry of air into the tangential filtration system. Additional sensors are available to monitor parameters like pH, temperature, conductivity, and UV absorbance.

Tangential filtration system FAQs

Below are answers to some frequently asked questions about tangential filtration systems.

What is a tangential flow filtration system?

A tangential flow filtration system comprises the components and functionality needed to filter or concentrate liquids such as cell lysates or microbial cell cultures. In upstream applications, for example, ÄKTA readyflux™ tangential flow filtration systems can be connected to bioreactor systems for use in clarification of cell culture feeds. In downstream applications, ÄKTA readyflux™ TFF systems can be connected to an ÄKTA ready™ single-use chromatography system for concentration and buffer exchange. Cytiva offers single-use and conventional TFF systems for a range of scales, as well as single-use and conventional hollow fiber cartridges.

 

What advantages does TFF have over NFF?

  • TFF prevents “filter cake” formation to allow continuous use.
  • In TFF, the process feed stays in the form of a mobile slurry that’s usable for further processing.
  • Unlike NFF, you can fractionate particles by size during TFF.

Why use TFF?

In TFF processes, the fluid that flows across the membrane easily rubs off particles on the surface to allow continuous operation.