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

Fluid flow and mixing in a novel intermittently rotating bioreactor for CAR-T cell therapy manufacturing
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用于 CAR-T 细胞疗法制造的新型间歇旋转生物反应器中的流体流动和混合

DOI:
10.1016/j.ces.2023.119175
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发表时间:
2023
影响因子:
4.7
通讯作者:
Atanasova G
Atanasova G
中科院分区:
工程技术2区
文献类型:
--
作者:
Atanasova G

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这项工作探索了目前用于自动化制造CAR-T细胞疗法的新型生物反应器中的混合和流体动力学,该疗法为多种形式的晚期血癌提供了单剂量治疗。圆柱形生物反应器具有低纵横比和自由表面。搅拌是通过整个容器围绕其中心轴的间歇旋转来实现的。到目前为止,尚未在生物处理背景下对该系统进行工程表征。本文研究了从静止转起和从静止转起的流体动力学问题。新的粒子图像测速和平面激光诱导荧光数据一起反射薄片的结果,脱落光的间歇旋转生物反应器内的不同瞬态流动区域,并确定宏观和微观混合的时间尺度。所呈现的结果可用于设计生物反应器的定制旋转模式,以改善细胞扩增步骤期间的混合性能。
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.
DOI: --
发表时间: 1981
影响因子: 3.7
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