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Solid-Solid Interfacial Contact of Tubing Walls Drives Therapeutic Protein Aggregation During Peristaltic Pumping

Fanthom, Thomas B; Wilson, Christopher; Gruber, David; Bracewell, Daniel G; (2023) Solid-Solid Interfacial Contact of Tubing Walls Drives Therapeutic Protein Aggregation During Peristaltic Pumping. Journal of Pharmaceutical Sciences 10.1016/j.xphs.2023.08.012. (In press). Green open access

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Abstract

Peristaltic pumping during bioprocessing can cause therapeutic protein loss and aggregation during use. Due to the complexity of this apparatus, root-cause mechanisms behind protein loss have been long sought. We have developed new methodologies isolating various peristaltic pump mechanisms to determine their effect on monomer loss. Closed-loops of peristaltic tubing were used to investigate the effects of peristaltic pump parameters on temperature and monomer loss, whilst two mechanism isolation methodologies are used to isolate occlusion and lateral expansion-relaxation of peristaltic tubing. Heat generated during peristaltic pumping can cause heat-induced monomer loss and the extent of heat gain is dependent on pump speed and tubing type. Peristaltic pump speed was inversely related to the rate of monomer loss whereby reducing speed 2.0-fold increased loss rates by 2.0- to 5.0-fold. Occlusion is a parameter that describes the amount of tubing compression during pumping. Varying this to start the contacting of inner tubing walls is a threshold that caused an immediate 20-30% additional monomer loss and turbidity increase. During occlusion, expansion-relaxation of solid-liquid interfaces and solid-solid interface contact of tubing walls can occur simultaneously. Using two mechanisms isolation methods, the latter mechanism was found to be most destructive and a function of solid-solid contact area, where increasing the contact area 2.0-fold increased monomer loss by 1.6-fold. We establish that a form of solid-solid contact mechanism whereby the contact solid interfaces disrupt adsorbed protein films is the root-cause behind monomer loss and protein aggregation during peristaltic pumping.

Type: Article
Title: Solid-Solid Interfacial Contact of Tubing Walls Drives Therapeutic Protein Aggregation During Peristaltic Pumping
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.xphs.2023.08.012
Publisher version: https://doi.org/10.1016/j.xphs.2023.08.012
Language: English
Additional information: © 2023 The Authors. Published by Elsevier Inc. on behalf of American Pharmacists Association under a Creative Commons license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Protein aggregation, Pumping, Peristaltic pump, Tubing, Interface, Contact, Stability, Antibody, Chromatography
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/10175730
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