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Co-current filtrate flow in TFF perfusion processes: Decoupling transmembrane pressure from crossflow to improve product sieving
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  • Patrick Romann,
  • Philip Giller,
  • Antony Sibilia,
  • Christoph Herwig,
  • Negin Nejatishahidein,
  • Arnaud Perilleux,
  • Jonathan Souquet,
  • Jean-Marc Bielser,
  • Thomas K. Villiger
Patrick Romann
Fachhochschule Nordwestschweiz FHNW - Campus Muttenz

Corresponding Author:[email protected]

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Philip Giller
Fachhochschule Nordwestschweiz FHNW - Campus Muttenz
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Antony Sibilia
Levitronix GmbH
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Christoph Herwig
Technische Universitat Wien
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Negin Nejatishahidein
The Pennsylvania State University Department of Chemical Engineering
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Arnaud Perilleux
Merck Serono SA Aubonne
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Jonathan Souquet
Merck Serono SA Aubonne
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Jean-Marc Bielser
Merck Serono SA Aubonne
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Thomas K. Villiger
Fachhochschule Nordwestschweiz FHNW - Campus Muttenz
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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.
06 Jul 2023Submitted to Biotechnology and Bioengineering
11 Jul 2023Submission Checks Completed
11 Jul 2023Assigned to Editor
11 Jul 2023Review(s) Completed, Editorial Evaluation Pending
15 Jul 2023Reviewer(s) Assigned
16 Aug 2023Editorial Decision: Revise Major
22 Aug 20231st Revision Received
23 Aug 2023Submission Checks Completed
23 Aug 2023Assigned to Editor
23 Aug 2023Review(s) Completed, Editorial Evaluation Pending
18 Sep 2023Reviewer(s) Assigned
01 Oct 2023Editorial Decision: Revise Minor
22 Oct 2023Review(s) Completed, Editorial Evaluation Pending
22 Oct 2023Editorial Decision: Accept