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理解瞬态在线尖峰系统中的停留时间分布:建模、实验与模拟

Understanding the Residence Time Distribution in a Transient Inline Spiking System: Modeling, Experiments, and Simulations.

作者信息

Hwang Minsun, Wang Junsuk, Jung Seon Yeop

机构信息

Department of Chemical Engineering, Dankook University, Yongin-si 16890, Gyeonggi-do, Republic of Korea.

出版信息

Membranes (Basel). 2023 Mar 25;13(4):375. doi: 10.3390/membranes13040375.

DOI:10.3390/membranes13040375
PMID:37103802
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10143522/
Abstract

A transient inline spiking system is a promising tool for evaluating the performance of a virus filter in continuous operation. For better implementation of the system, we performed a systematic analysis to understand the residence time distribution (RTD) of inert tracers in the system. We aimed to understand the RTD of a salt spike, not retained onto or within the membrane pore, to focus on its mixing and spreading within the processing units. A concentrated NaCl solution was spiked into a feed stream as the spiking duration (tspike) was varied from 1 to 40 min. A static mixer was employed to mix the salt spike with the feed stream, which then passed through a single-layered nylon membrane inserted in a filter holder. The RTD curve was obtained by measuring the conductivity of the collected samples. An analytical model, the PFR-2CSTR model, was employed to predict the outlet concentration from the system. The slope and peak of the RTD curves were well-aligned with the experimental findings when τPFR = 4.3 min, τCSTR1 = 4.1 min, and τCSTR2 = 1.0 min. CFD simulations were performed to describe the flow and transport of the inert tracers through the static mixer and the membrane filter. The RTD curve spanned more than 30 min, much longer than tspike, since solutes were dispersed within processing units. The flow characteristics in each processing unit correlated with the RTD curves. Our detailed analysis of the transient inline spiking system would be helpful for implementing this protocol in continuous bioprocessing.

摘要

瞬态在线加标系统是评估病毒过滤器连续运行性能的一种很有前景的工具。为了更好地实施该系统,我们进行了系统分析,以了解惰性示踪剂在系统中的停留时间分布(RTD)。我们旨在了解未保留在膜孔上或膜孔内的盐加标的RTD,以关注其在处理单元内的混合和扩散情况。随着加标持续时间(tspike)从1分钟变化到40分钟,将浓NaCl溶液加入进料流中。使用静态混合器将盐加标与进料流混合,然后进料流通过插入过滤器支架的单层尼龙膜。通过测量收集样品的电导率获得RTD曲线。采用解析模型PFR - 2CSTR模型来预测系统的出口浓度。当τPFR = 4.3分钟、τCSTR1 = 4.1分钟和τCSTR2 = 1.0分钟时,RTD曲线的斜率和峰值与实验结果吻合良好。进行了计算流体动力学(CFD)模拟,以描述惰性示踪剂通过静态混合器和膜过滤器的流动和传输情况。由于溶质在处理单元内分散,RTD曲线跨度超过30分钟,远长于tspike。每个处理单元中的流动特性与RTD曲线相关。我们对瞬态在线加标系统的详细分析将有助于在连续生物加工中实施该方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f325/10143522/a0237af40de4/membranes-13-00375-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f325/10143522/cf1e00a8b552/membranes-13-00375-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f325/10143522/2a5fda864bd4/membranes-13-00375-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f325/10143522/43e863f6ebf7/membranes-13-00375-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f325/10143522/afebe3b0ead2/membranes-13-00375-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f325/10143522/e1422dd50ca6/membranes-13-00375-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f325/10143522/9c22c70cb8f9/membranes-13-00375-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f325/10143522/49058ce28096/membranes-13-00375-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f325/10143522/ca1fd22feec7/membranes-13-00375-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f325/10143522/c7f53373ba06/membranes-13-00375-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f325/10143522/a0237af40de4/membranes-13-00375-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f325/10143522/cf1e00a8b552/membranes-13-00375-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f325/10143522/2a5fda864bd4/membranes-13-00375-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f325/10143522/43e863f6ebf7/membranes-13-00375-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f325/10143522/afebe3b0ead2/membranes-13-00375-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f325/10143522/e1422dd50ca6/membranes-13-00375-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f325/10143522/9c22c70cb8f9/membranes-13-00375-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f325/10143522/49058ce28096/membranes-13-00375-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f325/10143522/ca1fd22feec7/membranes-13-00375-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f325/10143522/c7f53373ba06/membranes-13-00375-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f325/10143522/a0237af40de4/membranes-13-00375-g010.jpg

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本文引用的文献

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Biotechnol Bioeng. 2022 Aug;119(8):2134-2141. doi: 10.1002/bit.28119. Epub 2022 May 5.
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Virus filtration: A review of current and future practices in bioprocessing.病毒过滤:生物工艺学中当前和未来实践的综述。
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