Eliminate the Recirculation Loop and Streamline Operations to Optimize Downstream Processing
Cadence Single-Pass TFF ( SPTFF ) is a patented breakthrough technology that allows direct flow-through concentration with no recirculation of product. SPTFF enables high concentration of shear sensitive proteins and antibodies >160 grams/liter. What makes this possible is a unique flow path design and staging of cassettes in a serial flow.
This exciting new technology leads to economic and practical benefits, including:
Increased yield of product due to improved recovery capability and lower hold-up volume.
Increased final product concentration due to high concentration factor capability.
Elimination of product damage or aggregation due to reduced residence time and shear exposure.
Ability to couple the concentration of product before or after other downstream process steps, consequently optimizing other steps and reducing in-process pool tank volumes.
Available in single use format.
Cadence single-pass TFF modules and systems can be easily integrated with other downstream processes such as chromatography or virus removal.
Using Cadence modules with Delta membrane, the innovative benefits of Single-Pass TFF technology are enhanced by the proven high flux, high selectivity, and low protein binding attributes of Delta regenerated cellulose membrane cassettes.
Optimize Economic and Operational Benefits
Enhance downstream processing to increase capacity and reduce costs – Cadence systems can eliminate or reduce intermediate storage tanks and associated cleaning of tanks when using the systems for in-process volume reduction before or after existing steps.
Increase yield and achieve high product recovery > 98 % – The single-pass TFF process collects most of the process volume during the process run, leaving only a small percentage of the product in the module at the end of the run. This small percentage of product can be easily recovered due to the low hold-up volume in the system.
Enable high concentration factors > 20X – High concentration factors are achieved due to the staging of cassettes in series, which results in high conversions of feed-to-permeate in one flow path. This is accomplished by optimizing the module staging configuration based on cassette performance for a particular application.
Optimize processing of highly shear-sensitive products – Processing results in only one pass through the pump and cassette, reducing shear exposure. For products sensitive to pumping, the pump can be completely eliminated by using pressurized vessels to flow the process fluid through the module. Further benefits are achieved by eliminating any mixing or foaming issues associated with the feed tank.
Use smaller, more compact systems – Cadence systems require less pump capacity, allowing smaller piping or tubing diameters for a more compact system design with lower working and hold-up volumes.
Simplify installation and use – Cadence modules are supplied preassembled. The modules’ feed, retentate and permeate ports are easily connected to clearly-marked system ports.
Innovative single-pass TFF processing takes place within Cadence modules. Cadence modules incorporate Pall’s proven T-Series cassettes with Delta membrane, and are available in different sizes to accommodate various processing volumes (see Ordering Information). Cadence modules are designed for use with a Pall Cadence single-pass TFF system. (Contact Pall for information on a Cadence system to meet your application requirements.)
Cadence Modules Incorporate High Performance T-Series Cassettes with Delta Membrane
Delta regenerated cellulose membrane offers high flux and selectivity. The membrane has been specifically developed to minimize protein binding to the surface and interstitial structure of the membrane. Inherently hydrophilic, this membrane shows low protein adsorption properties and is optimal for processes involving very hydrophilic proteins. Delta regenerated cellulose membrane shows low fouling characteristics, allowing consistent performance or flux from run to run. It is easy to clean and typically recovers normalized water permeability (NWP) by using 0.1 N NaOH.
Cadence single-pass TFF modules and systems are used tconcentrate biomolecules. They alscan be used for salt-level reduction by concentrating followed by in-line dilution. Volume capacities range from several liters tthousands of liters. Single-pass TFF may be used tperform various steps in a wide range of applications in the biopharmaceutical industry, including:
In-process volume reduction
Desalting protein solutions
Purification and recovery of antibodies or recombinant proteins
Preparation of samples (concentrating, desalting) before or after column chromatography
Depending on the application, Cadence modules may alsbe applied for single use. When applied for single use, Cadence modules are used with a specially-designed Cadence system. Contact Pall for more information on single-use systems.
The commercialization of a revolutionary TFF technology by Pall Life Sciences presents opportunities tsimplify biopharmaceutical process design and lower capital and operational costs. The new technology, single-pass TFF, is brought tlife through Pall’s Cadence systems and modules. This Application Note introduces the design innovations of Cadence single-pass TFF systems tbiopharmaceutical researchers and manufacturers.
SPTFF process is continuous, produces high concentration factors, significantly higher conversion in one pass through flow rating control and eliminates the need for the conventional recirculation loop.
Elimination of the conventional recirculation loop minimizes aggregation problems and requires no mixing, minimizes shear exposure and also alows the SPTFF step to be coupled with other downstream process steps.
Additional SPTFF benefits over conventional TFF include lower system hold-up volumes, higher recoveries, and lower flush volume requirements.
Applications that can leverage SPTFF technology include but are not limited tin-process volume reduction, inline salt reduction, high-concentration formulations, and processing of fragile biomolecules.
The operating conditions and module configurations for any single-pass TFF process must be established by performing trials and analyzing results. Pall’s Technical Support Group is available to assist in conducting trials to select configurations and develop operating conditions necessary to achieve the desired process objectives.
Cadence Module Materials of Construction
Delta regenerated cellulose, 10 kD and 30 kD
Polyurethane with white pigment (TiO2)
Medical grade, platinum cured silicone
Medical grade, platinum cured silicone
Cadence Module Operating Limits
6 barg (87 psig) @ 23 °C 4.1 barg (60 psig) @ 55 °C
Maximum Transmembrane Pressure (TMP)
4.1 barg (60 psig) @ 4 - 55 °C
Processing Temperature Range
4 to 40 °C (freezing will damage module)
2 to 13
Flow Rate Range During Cleaning
< 5 L/min/m2 (0.2 L/min/ft2)
The performance of Cadence modules, based on an IgG model feed solution, is demonstrated in the table below over a wide range of feed flow rates (L/min/m2) and volumetric concentration factors (X) for various module configurations and feed concentrations (g/L).
Cadence Module Typical Feed Flow Rates in L/min/m2
* LMH = Liters/meter2/hour
Cadence Module Integrity Test
Systems Integrity Test Pressure
4.1 barg (60 psig)
Acceptable Pressure Decay (System)
< 0.07 barg (1 psig) per minute
Module Integrity Test Pressure
4.1 barg (60 psig)
Acceptable Forward Flow Rate
< 50 sccm/ft2 (538 sccm/m2)
Each Cadence module has a unique serial number for full traceability.
The shelf life of Cadence modules packaged in preservative is expected to be two years from the date of manufacture when the modules are stored unopened in the original packaging at ambient temperature up to 25 °C and protected from direct light. Extended shelf life studies are ongoing.
Materials of construction for Cadence modules have been tested and meet the requirements for the Biological Reactivity Tests listed in the United States Pharmacopeia (USP) under USP <88> for Class VI - 70 °C Plastics.
Each module is supplied with the following comprehensive documentation to ensure the Cadence module is operated successfully:
Certificate of Quality
Care and Use Procedures
Material Safety Data Sheet for the module preservative
Contact your local Pall representative to obtain:
Validation service for specific tests such as compatibility testing with your product fluid
Training and technical support to optimize your process using Cadence systems
Pall Provides Comprehensive Documentation with Each Cadence Module
and order Cadence modules using the table below. For example, a Cadence T01 module with 10 kD Delta regenerated cellulose membrane area of 0.14 m2 (1.5 ft2) is part number CD010T010815. Note: a Pall Cadence system must be used to operate Cadence modules. (Contact Pall for information on a Cadence system to meet your application requirements.)