{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T04:40:33Z","timestamp":1781930433125,"version":"3.54.5"},"reference-count":95,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T00:00:00Z","timestamp":1727395200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000046","name":"National Research Council Canada","doi-asserted-by":"publisher","award":["PR\u2010023\u20101"],"award-info":[{"award-number":["PR\u2010023\u20101"]}],"id":[{"id":"10.13039\/501100000046","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN\u201040482021"],"award-info":[{"award-number":["RGPIN\u201040482021"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aiche.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biotechnology Progress"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Technology scale\u2010up and transfer are a fundamental and critical part of process development in biomanufacturing. Important bioreactor hydrodynamic characteristics such as working volume, overhead gas flow rate, volumetric power input (P\/V), impeller type, agitation regimen, sparging aeration strategy, sparger type, and k\n                    <jats:sub>L<\/jats:sub>\n                    a must be selected based on key performance indicators (KPI) to ensure a smooth and seamless process scale\u2010up and transfer. Finding suitable operational setpoints and developing an efficient feeding regimen to ensure process efficacy and consistency are instrumental. In this investigation, process development of a cumate inducible Chinese hamster ovary (CHO) stable pool expressing trimeric SARS\u2010CoV\u20102 spike protein in 1.8\u2009L benchtop stirred\u2010tank bioreactors is detailed. Various dissolved oxygen levels and aeration air caps were studied to determine their impact on cell growth and metabolism, culture longevity, and endpoint product titers. Once hydrodynamic conditions were tuned to an optimal zone, various feeding strategies were explored to increase culture performance. Dynamic feedings such as feeding based on current culture volume, viable cell density (VCD), oxygen uptake rate (OUR), and bio\u2010capacitance signals were tested and compared to standard bolus addition. Increases in integral of viable cell concentration (IVCC) (1.25\u2010fold) and protein yield (2.52\u2010fold), as well as greater culture longevity (extension of 5\u2009days) were observed in dynamic feeding strategies when compared to periodic bolus feeding. Our study emphasizes the benefits of designing feeding strategies around metabolically relevant signals such as OUR and bio\u2010capacitance signals.\n                  <\/jats:p>","DOI":"10.1002\/btpr.3507","type":"journal-article","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T07:35:08Z","timestamp":1727422508000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["<scp>CHO<\/scp>\n                    stable pool fed\u2010batch process development of\n                    <scp>SARS<\/scp>\n                    \u2010\n                    <scp>CoV<\/scp>\n                    \u20102 spike protein production: Impact of aeration conditions and feeding strategies"],"prefix":"10.1002","volume":"41","author":[{"given":"Sebastian\u2010Juan","family":"Reyes","sequence":"first","affiliation":[{"name":"Department of Chemical Engineering Polytechnique Montreal  Quebec Canada"},{"name":"Human Health Therapeutics Research Centre National Research Council Canada  Montr\u00e9al, Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phuong Lan","family":"Pham","sequence":"additional","affiliation":[{"name":"Human Health Therapeutics Research Centre National Research Council Canada  Montr\u00e9al, Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Durocher","sequence":"additional","affiliation":[{"name":"Human Health Therapeutics Research Centre National Research Council Canada  Montr\u00e9al, Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2106-1331","authenticated-orcid":false,"given":"Olivier","family":"Henry","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering Polytechnique Montreal  Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,27]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2016.06.005"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2020.12.005"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.28387"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.469"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bej.2020.107870"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/pr10020189"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.25684"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.425"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.1845"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jctb.4522"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.2782"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2011.03.002"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253\u2010018\u20109388\u20104"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.201700607"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.28032"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253\u2010016\u20107380\u20104"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11121929"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.24858"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.436"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1369\u2010703X(02)00028\u20101"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1097\u20100290(19960720)51:2<206::Aid\u2010bit10>3.0.Co;2\u2010k"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1389\u20101723(99)89025\u20102"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-019-09989-4"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2019.00195"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/pr9112073"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2011.05.024"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2017.06.009"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/1472\u20106750\u20106\u201043"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-79871-0_12"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2008.10.006"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.2743"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12249-019-1451-7"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.compchemeng.2019.106693"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.25330"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/bp0256263"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/bp970078s"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.201100153"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10616-008-9160-1"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1007917409455"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.20875"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.27124"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253\u2010022\u201012342\u2010x"},{"key":"e_1_2_10_44_1","unstructured":"Signal: Signal processing.2014.http:\/\/r\u2010forge.r\u2010project.org\/projects\/signal\/."},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.2489"},{"key":"e_1_2_10_46_1","first-page":"191","volume-title":"Systematic development of temperature shift strategies for Chinese hamster ovary cells based on short duration cultures and kinetic modeling","author":"Xu J","year":"2019"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10616\u2010012\u20109446\u20101"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bej.2018.01.031"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12934-014-0181-5"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.646"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.1995.1225"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2016.07.004"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.3220"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.1647"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2019.00078"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.26232"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2019.00076"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2017.7216"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.TM117.000239"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bej.2013.11.010"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.201700499"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.202100098"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymben.2005.10.002"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.23586"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-815409-0.00012-7"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-1656(02)00011-1"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.22643"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiosc.2017.11.002"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2012.08.021"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.3390\/life11090945"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0076611"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.3001"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.398"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.1042\/ba20030170"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.260390511"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2013.01.025"},{"key":"e_1_2_10_77_1","doi-asserted-by":"publisher","DOI":"10.4155\/pbp.13.56"},{"key":"e_1_2_10_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mec.2021.e00179"},{"key":"e_1_2_10_79_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.24983"},{"key":"e_1_2_10_80_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.27247"},{"key":"e_1_2_10_81_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.27495"},{"key":"e_1_2_10_82_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr501027c"},{"key":"e_1_2_10_83_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.24826"},{"key":"e_1_2_10_84_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.201400664"},{"key":"e_1_2_10_85_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.23269"},{"key":"e_1_2_10_86_1","doi-asserted-by":"publisher","DOI":"10.2174\/2213235X06666180803112546"},{"key":"e_1_2_10_87_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-021-11755-4"},{"key":"e_1_2_10_88_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes14081576"},{"key":"e_1_2_10_89_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.27993"},{"key":"e_1_2_10_90_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10616\u2010014\u20109720\u20105"},{"key":"e_1_2_10_91_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.procbio.2011.03.014"},{"key":"e_1_2_10_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bej.2016.06.031"},{"key":"e_1_2_10_93_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253\u2010017\u20108531\u2010y"},{"key":"e_1_2_10_94_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2022.108048"},{"key":"e_1_2_10_95_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-019-02096-3"},{"key":"e_1_2_10_96_1","unstructured":"ReyesSJ KeeblerM SchulteA et al.Impact of protein production on metabolic activity of CHO stable cell line producing palivizumab. Kuhner. Accessed 2024\u201004\u201012 2024.https:\/\/kuhner.com\/wAssets\/docs\/download\/Poster\/Poster-NRC\/TOM_Antibody_Poster-4_NRC-Kuhner.pdf"}],"container-title":["Biotechnology Progress"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aiche.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/btpr.3507","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T09:32:35Z","timestamp":1761557555000},"score":1,"resource":{"primary":{"URL":"https:\/\/aiche.onlinelibrary.wiley.com\/doi\/10.1002\/btpr.3507"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,27]]},"references-count":95,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1002\/btpr.3507"],"URL":"https:\/\/doi.org\/10.1002\/btpr.3507","archive":["Portico"],"relation":{},"ISSN":["8756-7938","1520-6033"],"issn-type":[{"value":"8756-7938","type":"print"},{"value":"1520-6033","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,27]]},"assertion":[{"value":"2024-06-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e3507"}}