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Fluid flow and mixing in a novel intermittently rotating bioreactor for CAR-T cell therapy manufacturing

Atanasova, GG; Micheletti, M; Ducci, A; (2023) Fluid flow and mixing in a novel intermittently rotating bioreactor for CAR-T cell therapy manufacturing. Chemical Engineering Science , 281 , Article 119175. 10.1016/j.ces.2023.119175. Green open access

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Abstract

This work explores the mixing and fluid dynamics in a novel bioreactor currently used for the automated manufacturing of CAR-T cell therapy, which offers a single-dose cure for several forms of advanced blood cancer. The cylindrical bioreactor has a low aspect ratio and a free surface. Agitation is achieved by intermittent rotation of the entire vessel around its central axis. No engineering characterisation has been conducted to date for this system in a bioprocessing context. The study examines the fluid dynamics problems of spin-up from rest and spin-down to rest. Novel Particle Image Velocimetry and Planar Laser-Induced Fluorescence data is presented alongside reflective flakes results, shedding light on the different transient flow regions inside the intermittently rotating bioreactor, and determining the timescales of macro- and micromixing. The results presented can be used to design a custom rotation pattern of the bioreactor for improved mixing performance during the cell expansion step.

Type: Article
Title: Fluid flow and mixing in a novel intermittently rotating bioreactor for CAR-T cell therapy manufacturing
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ces.2023.119175
Publisher version: https://doi.org/10.1016/j.ces.2023.119175
Language: English
Additional information: © 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: CliniMACS Prodigy®, Intermittent agitation, Mixing without an impeller, Taylor-Gortler ¨ instabilities, CAR-T manufacturing
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
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Mechanical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/10175747
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