{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:03:51Z","timestamp":1792015431410,"version":"4.4.0"},"reference-count":34,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T00:00:00Z","timestamp":1645660800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Engineering in Life Sciences"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Monoclonal antibodies (mAbs) are of great interest to the biopharmaceutical industry due to their widely used application as human therapeutic and diagnostic agents. As such, mAb require to exhibit human\u2010like glycolization patterns. Therefore, recombinant Chinese hamster ovary (CHO) cells are the favored production organisms; many relevant biopharmaceuticals are already produced by this cell type. To optimize the mAb yield in CHO DG44 cells a corelation between stress\u2010induced cell size expansion and increased specific productivity was investigated. CO<jats:sub>2<\/jats:sub> and macronutrient supply of the cells during a 12\u2010day fed\u2010batch cultivation process were tested as stress factors. Shake flasks (500\u00a0mL) and a small\u2010scale bioreactor system (15\u00a0mL) were used for the cultivation experiments and compared in terms of their effect on cell diameter, integral viable cell concentration (IVCC), and cell\u2010specific productivity. The achieved stress\u2010induced increase in cell\u2010specific productivity of up to 94.94.9%\u2013134.4% correlates to a cell diameter shift of up to 7.34\u00a0\u03bcm. The highest final product titer of 4\u00a0g\/L was reached by glucose oversupply during the batch phase of the process.<\/jats:p>","DOI":"10.1002\/elsc.202100062","type":"journal-article","created":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T07:22:51Z","timestamp":1645687371000},"page":"427-436","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Stress\u2010induced increase of monoclonal antibody production in CHO cells"],"prefix":"10.1002","volume":"22","author":[{"given":"Jana","family":"Schellenberg","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Technische Chemie Leibniz Universit\u00e4t Hannover  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamanna","family":"Nagraik","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Technische Chemie Leibniz Universit\u00e4t Hannover  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ole Jacob","family":"Wohlenberg","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Technische Chemie Leibniz Universit\u00e4t Hannover  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Ruhl","sequence":"additional","affiliation":[{"name":"Field Application Specialist \u2013 Cell Culture Technologies Sartorius Stedim Biotech GmbH  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janina","family":"Bahnemann","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Technische Chemie Leibniz Universit\u00e4t Hannover  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Scheper","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Technische Chemie Leibniz Universit\u00e4t Hannover  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00f6rte","family":"Solle","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Technische Chemie Leibniz Universit\u00e4t Hannover  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,2,24]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"Biomanufacturing Technology Roadmap\u2010Modular and Mobile","author":"Moyle D","year":"2017"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-011-3758-5"},{"issue":"10","key":"e_1_2_9_4_1","first-page":"40","article-title":"Recombinant protein therapeutics from CHO Cells \u2010 20 years and counting","volume":"103","author":"Karthik P Jayapal","year":"2007","journal-title":"Chemical Engineering Progress"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.200800264"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-016-7388-9"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.436"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv475"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/1753-6561-5-S8-P105"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.23289"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2016.06.019"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.2757"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.23072"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00449-017-1790-2"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/1753-6561-5-S8-P122"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40643-015-0072-6"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.25529"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2018.04.011"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/elsc.202000056"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/elsc.202000049"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-017-8531-y"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2012.03.004"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.201100143"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.25141"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbf.1003"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.meteno.2015.06.001"},{"key":"e_1_2_9_27_1","volume-title":"Cell Culture Engineering XVI","author":"Martens D","year":"2018"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.21076"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02933001"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6750-14-15"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.22041"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-59745-399-8_12"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10616-007-9089-9"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.procbio.2017.11.013"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.23031"}],"container-title":["Engineering in Life Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/elsc.202100062","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/elsc.202100062","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/elsc.202100062","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T18:40:50Z","timestamp":1760553650000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/elsc.202100062"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,24]]},"references-count":34,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,5]]}},"alternative-id":["10.1002\/elsc.202100062"],"URL":"https:\/\/doi.org\/10.1002\/elsc.202100062","archive":["Portico"],"relation":{},"ISSN":["1618-0240","1618-2863"],"issn-type":[{"value":"1618-0240","type":"print"},{"value":"1618-2863","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,24]]},"assertion":[{"value":"2021-06-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}