Scale-up Tangential Flow Filtration Technology

Tangential Flow Filtration (TFF) is a rapid and efficient method for separation and purification of biomolecules. It can be applied to a wide range of biological fields, such as immunology, protein chemistry, molecular biology, biochemistry, and microbiology. TFF can be used to concentrate and desalt sample solutions ranging in volume from 10 mL to thousands of liters. It can be used to fractionate large from small biomolecules, harvest cell suspensions and clarify fermentation broths and cell lysates. Selecting the right TFF technology Pall offers two main technology platforms for scale-up in tangential flow filtration: flat-sheet cassette technology, and hollow fiber technology. Each technology platform incorporates a range of flow channel configurations and membrane chemistries, providing customers with the widest choice of options to meet specific processing objectives. Use the schematic below to select the most appropriate platform and configuration for your application.

Pall offers a broad range of membrane cassettes for TFF to cover the growing range of potential applications and process volumes.

It is important to consider your specific requirements in order to select the most appropriate cassette and format for your application.

Membrane Area Requirements

The process volume and concentration, filtrate flux rate and time requirements must all be considered in order to determine the membrane area required for a specific process. Specify range of expected volumes and calculate area based on largest volume.

• Filtrate Volume — total filtrate volume collected from concentration and diafiltration steps. Filtrate volume can be estimated from the total process volume, concentration factor and diafiltration volumes required
• Time Requirements — specify the maximum allowable process time
• Filtrate Flux Rate (FFR) — the rate of liquid passing through the membrane; e.g. L/m²/h (LMH). Trials are required to determine the actual FFR for a product under a specified set of operating parameters including transmembrane pressure (TMP), cross flow flux rate (CFF) and temperature

To estimate membrane area required for a process, use the following equation:

Required Membrane Area = filtrate volume ÷ [average filtrate flux rate x process time]

From the Required Membrane Area calculated, a cassette holder with sufficient capacity can be selected.

Scale-Up and Scale-Down

Processes are generally developed on a scaled-down system to conserve sample. Ideally, small-scale testing should be performed using a cassette format that has the same pathlength and channel configuration as the full scale system.

This allows direct scale-up by the application of a simple rule: increase membrane area and retentate flow rate in direct proportion to any increase in sample volume. When this formula is applied, the TMP, Cross Flow Flux Rate and process time will not change appreciably. However if pathlength is changed, then additional optimization will be required.