Flow and residence time distribution in small-scale dual-layer depth filter capsules

Kim, Min-Young; Nejatishahidein, Negin; Borujeni, Ehsan Espah; Roush, David J.; Zydney, Andrew L.; Borhan, Ali

doi:10.1016/j.memsci.2020.118625

Cited by 10 publications

(14 citation statements)

References 20 publications

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“…The results were independent of the filtrate flux over the range of conditions of interest in these depth filtration modules due to the low Reynolds numbers. As described by Kim et al (2021), more than 60% of the total flow in the Supracap TM 50 capsule follows the radial bypass, with bypass through Path 4 accounting for more than half of the flow. In contrast, nearly all of the flow (97.2%) in the Stax TM module follows the ideal flow path (Path 2), with the largest bypass through Path 4 accounting for only 2.4% of total flow.…”

Section: Resultsmentioning

confidence: 87%

“…The computed dye concentrations are in qualitative agreement with the experimental data in both modules, properly capturing both the initial breakthrough and the subsequent rapid increase in the exit concentration. The results for the Supracap TM 50 in the absence of binding have been discussed in detail by Kim et al (2021). Binding interactions have little effect on the initial breakthrough behavior, but the dye concentration at long times ( t > 100 min) is reduced as k a increases, that is, as binding becomes more pronounced.…”

Section: Resultsmentioning

confidence: 87%

“…Layers are numbered in the order in which they are housed within the capsule as shown in Figure 1, with bottom and top referring to the upper and lower surfaces of each layer based on the configuration in the modules. Images for the Supracap TM 50 are taken from Kim et al (2021)…”

Section: Resultsmentioning

confidence: 99%

“…The RTD was evaluated using Cibacron blue dye (Sigma-Aldrich, B1064) dissolved in DI water at a concentration of 0.1 g/L for the large-scale module and at 3 g/L for the small-scale capsule following the procedures described by Kim et al (2021). It was impractical to use the higher dye concentration in the Stax TM module due to material constraints associated with the very large feed volumes.…”

Section: Rtdmentioning

confidence: 99%

“…The objective of this study was to extend our previous studies of the Supracap TM 50 module (Jung et al, 2021; Kim et al, 2021; Nejatishahidein et al, 2020) to specifically examine the difference in performance between this lab‐scale module and the pilot‐scale Stax™ capsule, both of which employ two layers of different grade PDH4 depth filtration media. The flow distributions were evaluated using CFD and validated using dye‐binding studies and RTD measurements obtained with a small dye.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Scale‐up issues for commercial depth filters in bioprocessing

Nejatishahidein

Kim

Jung

et al. 2022

Biotech & Bioengineering

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Significant increases in cell density and product titer have led to renewed interest in the application of depth filtration for initial clarification of cell culture fluid in antibody production. The performance of these depth filters will depend on the local pressure and velocity distribution within the filter capsule, but these are very difficult to probe experimentally, leading to challenges in both process design and scale‐up. We have used a combination of carefully designed experimental studies and computational fluid dynamics (CFD) to examine these issues in both lab‐scale (SupracapTM 50) and pilot‐scale (StaxTM) depth filter modules, both employing dual‐layer lenticular PDH4 media containing diatomaceous earth. The SupracapTM 50 showed a more rapid increase in transmembrane pressure and a more rapid DNA breakthrough during filtration of a Chinese Hamster Ovary cell culture fluid. These results were explained using CFD calculations which showed very different flow distributions within the modules. CFD predictions were further validated using measurements of the residence time distribution and dye binding in both the lab‐scale and pilot‐plant modules. These results provide important insights into the factors controlling the performance and scale‐up of these commercially important depth filters as well as a framework that can be broadly applied to develop more effective depth filters and depth filtration processes.

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Section: Resultsmentioning

confidence: 87%

Section: Resultsmentioning

confidence: 87%

Section: Resultsmentioning

confidence: 99%

Section: Rtdmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Scale‐up issues for commercial depth filters in bioprocessing

Nejatishahidein

Kim

Jung

et al. 2022

Biotech & Bioengineering

Self Cite

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Leveraging mathematical models for optimizing filter utility at manufacturing scale

Rose

Dhingra

Joseph

et al. 2023

Biotech & Bioengineering

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In the production of biopharmaceuticals depth filters followed by sterile filters are often employed to remove residual cell debris present in the feed stream. In the back drop of a global pandemic, supply chains associated with the production of biopharmaceuticals have been constrained. These constraints have limited the available amount of depth filters for the manufacture of biologics. This has placed manufacturing facilities in a difficult position having to choose between running processes with reduced number of depth filters and risking a failed batch or the prospect of plants going into temporary shutdown until the depth filter resources are replenished. This communication describes a modeling based method that leverages manufacturing scale filtration data to predict the depth filter performance with a reduced number of filters and an increased operational flux. This method can be used to quantify the acceptable level of area reduction before which the filtration process performance is affected. This enables facilities to manage their filter inventory avoiding potential plant shutdowns and reduces the risks of negative depth filter performance.

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