Fluid dynamics and mixing in a novel intermittently rotating bioreactor for CAR-T cell therapy: Spin-down from incomplete spin-up

Abstract

This work explores the fluid flow and mixing within a new type of intermittently rotating bioreactor used for the automated manufacturing of CAR-T cell therapy products; CAR-T is a novel cell-based gene therapy which offers a single-dose cure for several forms of advanced blood cancer. The rotating cylinder bioreactor has a free surface and a liquid height to radius ratio of 0.5. Agitation is achieved via intermittent rotation of the entire vessel around its central vertical axis. No comprehensive engineering characterisation of the fluid dynamics in a bioprocessing context exists to date for this type of bioreactor. The present study examines the fluid dynamics and mixing during spin-down to rest following incomplete spin-up (i.e. the starting state of the fluid is not solid body rotation). Novel Particle Image Velocimetry (PIV) and Planar Laser-Induced Fluorescence (PLIF) data is presented, shedding light on the different transient flow regions inside the intermittently rotating bioreactor, and on the impact spin-up time has on the mixing efficiency of the subsequent spin-down stage. The results presented can be used to inform the design of a custom intermittent agitation pattern for any resembling cylinder bioreactors, the adoption of which could lead to higher yields and reduced costs for the cell expansion step of the manufacturing process.