Inline Concentration TFF UF/DF: From SPTFF to SSTFF

Traditional TFF Technology and The Single Pass TFF (SPTFF)

Tangential Flow Filtration (TFF) has long been a cornerstone technology in bioprocessing, particularly for the concentration and diafiltration of protein solutions. In traditional TFF systems, the feed solution flows tangentially across a semi-permeable membrane, which allows solvent and small molecules to pass through while retaining larger biomolecules like proteins. This approach reduces membrane fouling/gel polarization and significantly improved UF/DF processing. Over the years, innovations like Single Pass Tangential Flow Filtration (SPTFF) have emerged, promising to simplify protein concentration directly in-line—without the need for recirculating loops or hold tanks.

The Obstacles of Running SPTFF for Practical Use

SPTFF quickly gained traction as the state-of-the-art solution for TFF, claiming inline UF/DF for concentration and diafiltration, especially in continuous or intensified bioprocessing environments. The concept is appealing: concentrate a protein solution in a single pass through a TFF module, eliminating recirculation flow and the tank simplifying the equipment and process setup. However, practical implementation has often fallen short of expectations. The fundamental challenge lies in severe gel layer polarization that builds up rapidly in SPTFF, not to mention the difficulty of controlling pressure and flow in the process. This ultimately leads to poor yield and inconsistent performance—undermining the very efficiency it aims to deliver. When it comes to connecting TFF to chromatography, the practical difficulty in controlling pressure/flow for both SSTFF and the chromatography renders it impossible to be applied as claimed by the SPTFF technology.

The Solution: SSTFF Instead Of SPTFF

At Lisure it is discovered that the key to making inline concentration truly feasible isn’t SPTFF, but a different approach called SSTFF (Steady-State Tangential Flow Filtration). Unlike SPTFF, SSTFF is designed to maintain a true steady-state operational mode, with control architecture that decouples the interdependent relationship between crossflow and TMP. This separation allows for much desirable control of mass transfer and shear conditions in TFF, drastically minimizing gel polarization and maintaining consistent performance over time.

Lisure’s patented SSTFF technology marks a breakthrough in ultrafiltration/diafiltration process design. By decoupling the driving forces of crossflow and TMP, SSTFF ensures that optimal operating parameters can be maintained throughout the run—something that SPTFF inherently cannot achieve. This advancement has opened the door to truly practical inline concentration solutions for proteins and other biomolecules, offering enhanced yield, process reliability, and scalability.

The Future Of TFF and Inline Concentration Using UF/DF

In the era of process intensification and continuous manufacturing, SSTFF stands as a robust alternative to legacy filtration methods. The critical implication of SSTFF is also the connectivity it provides to allow chromatography process to connect to TFF or vise versa, a foundational piece of connected batches and continuous processes. For companies seeking to reduce footprint, increase throughput, and simplify operations, embracing SSTFF over SPTFF may be the shift needed to unlock the full potential of inline ultrafiltration and diafiltration, connected batch for multiple steps, and complete continuous bioprocesses.