2018
DOI: 10.1002/bit.26811
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Abstract: In this study, we investigated the effects of alternating tangential flow (ATF) cell separation on high-density perfusion cultures. We have developed methods to estimate theoretical residence times of cells in the ATF system and discovered that long residence times (above 75 s) correlate with decreased growth, metabolism, and productivity. We have calculated energy dissipation rates in the ATF transfer line and filter and empirically studied the impacts of increased exchange rates on cell culture, determining … Show more

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Cited by 34 publications
(35 citation statements)
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“…In continuous perfusion cultures that maintain a cell culture at minimal growth rates, a constant, low cell bleed rate may also serve to continuously remove accumulated biomass debris resulting mostly from cell death due to some process insult (e.g. bubble damage, hydrodynamic shear, and so forth; Walther, McLarty, & Johnson, ).…”
Section: Introductionmentioning
confidence: 99%
See 1 more Smart Citation
“…In continuous perfusion cultures that maintain a cell culture at minimal growth rates, a constant, low cell bleed rate may also serve to continuously remove accumulated biomass debris resulting mostly from cell death due to some process insult (e.g. bubble damage, hydrodynamic shear, and so forth; Walther, McLarty, & Johnson, ).…”
Section: Introductionmentioning
confidence: 99%
“…As a result, conventional continuous perfusion cell culture systems usually have working volumes below 2,000 L, and if operated under conditions where productivity is highest (e.g. high viable cell densities and usually high perfusion rates), require frequent change out of the membrane‐based cell retention device due to fouling (Mercille et al, ; Walther, McLarty et al, ; Woodside, Bowen, & Piret, ). Additionally, cell retention devices capable of generating very large volumes of cell‐free culture harvest can be quite complex and expensive, damaging to cells through excessive shear forces, and prone to failure (Castilho & Medronho, ; Chotteau, ; Woodside et al, ).…”
Section: Introductionmentioning
confidence: 99%
“…Despite the variation observed in Experiment 2, a settling time longer than 40 min was still well‐tolerated by this cell line, high quality product could still be achieved. The microscale perfusion mimicking setup did not negatively impact product quality as ATF bench scale perfusion environments were reported to do so (W. Kelly et al, ; Walther, McLarty, & Johnson, ).…”
Section: Resultsmentioning
confidence: 93%
“…The microscale perfusion mimicking setup did not negatively impact product quality as ATF bench scale perfusion environments were reported to do so (W. Kelly et al, 2014;Walther, McLarty, & Johnson, 2019).…”
Section: Productivity and Product Qualitymentioning
confidence: 98%
“…During continuous harvesting this can cause pore narrowing and eventually membrane blockage. In the recent years, numerous studies have reported on such unwanted filter fouling even when large-pore hollow fiber membranes have been applied (Bolton & Apostolidis, 2017;Genzel et al, 2014;Nikolay, Castilho, Reichl, & Genzel, 2018;Nikolay, Léon, Schwamborn, Genzel, & Reichl, 2018;Walther, McLarty, & Johnson, 2018;S. Wang et al, 2017).…”
Section: Introductionmentioning
confidence: 99%