A Microfluidic TFF Device for Biopharmaceutical Process Development: Scale‐Down Verification of Ultrafiltration and Diafiltration Modes for Monoclonal Antibodies

ABSTRACT

Tangential flow filtration (TFF) is an essential operation in downstream bioprocessing, yet conventional scale‐down models require large material volumes and often fail to capture scale‐relevant hydrodynamics. A microfluidic TFF (µTFF) platform was developed that preserves wall shear rate and transmembrane pressure, enabling low‐volume investigation of UF/DF processes. Through iterative design of channel geometry and membrane selection, the final device achieved stable operation, high recovery, and a reduced runtime of 2.33 h from feed volumes as low as 10 mL for UF and 1 mL for DF. When operated at matched shear, the µTFF platform captured key bench‐scale filtration characteristics, including filtration time, TMP behavior, permeate‐flux profiles, and yields above 88% with negligible permeate loss. The device also resolved membrane‐dependent behavior across PES and RC chemistries, showing consistent cross‐scale trends for PES membranes while highlighting the influence of membrane‐specific variability on RC membrane performance and cross‐scale comparability. Validated with BSA and subsequently with monoclonal antibodies, the µTFF system demonstrated reproducible buffer exchange, maintained protein integrity, and replicated key transport phenomena. Its low working volumes, rapid turnaround, and ability to maintain scale‐relevant hydrodynamics position the µTFF platform as a high‐throughput screening tool for TFF process optimization, supporting faster development cycles and evaluation of purification strategies.