Co-current filtrate flow in TFF perfusion processes: Decoupling
transmembrane pressure from crossflow to improve product sieving
Abstract
Hollow fiber-based membrane filtration has emerged as the dominant
technology for cell retention in perfusion processes yet significant
challenges in alleviating filter fouling remain unsolved. In this work,
the benefits of co-current filtrate flow applied to a tangential flow
filtration (TFF) module to reduce or even completely remove Starling
recirculation caused by the axial pressure drop within the module was
studied by pressure characterization experiments and perfusion cell
culture runs. Additionally, a novel concept to achieve alternating
Starling flow within unidirectional TFF was investigated. Pressure
profiles demonstrated that precise flow control can be achieved with
both lab-scale and manufacturing scale filters. TFF systems with
co-current flow showed up to 40% higher product sieving compared to
standard TFF. The decoupling of transmembrane pressure from crossflow
velocity and filter characteristics in co-current TFF alleviates common
challenges for hollow-fiber based systems such as limited crossflow
rates and relatively short filter module lengths, both of which are
currently used to avoid extensive pressure drop along the filtration
module. Therefore, co-current filtrate flow in unidirectional TFF
systems represents an interesting and scalable alternative to standard
TFF or alternating TFF operation with additional possibilities to
control Starling recirculation flow.