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Despite their broad application in academia and industry, shake flasks usually lack standardized and user\u2010friendly online monitoring techniques. In this work, the <jats:bold>pH<\/jats:bold> and Respiratory Activity MOnitoring System (pH\u2010RAMOS) for the non\u2010invasive online measurement of the oxygen transfer rate (OTR), carbon dioxide transfer rate (CTR), and pH in up to eight parallel shake flasks under sterile conditions is presented. The OTR and CTR are quasi\u2010continuously measured in the headspace of the shake flasks using dedicated oxygen and carbon dioxide sensors, enabling precise respiratory quotient (RQ) evaluation. Self\u2010adhesive pH sensor spots are used for the high\u2010frequent real\u2010time pH monitoring of the culture. These prototype pH sensor spots stand out due to their simple sterilizability and subsequent one\u2010point calibration in the cultivation medium. The long\u2010term stability of the pH sensor spots was assessed in a 28\u2010day long abiotic experiment. The novel pH\u2010RAMOS was validated with different eukaryotic and prokaryotic microorganisms, such as <jats:italic>Ogataea polymorpha<\/jats:italic>, <jats:italic>Ustilago trichophora<\/jats:italic>, and <jats:italic>Vibrio natriegens<\/jats:italic>. The combination of online OTR, CTR, RQ, and pH signals allowed for identifying various metabolic phenomena, such as oxygen limitations, substrate limitations, diauxies, and the production or consumption of specific compounds, based on their degree of reduction or change of pH. The high\u2010frequent and sensitive pH\u2010monitoring was particularly advantageous for registering subtle and transient metabolic phenomena.<\/jats:p>","DOI":"10.1002\/btpr.3525","type":"journal-article","created":{"date-parts":[[2024,12,13]],"date-time":"2024-12-13T03:50:51Z","timestamp":1734061851000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["High\u2010sensitivity real\u2010time monitoring of <scp>pH<\/scp> and respiration activity unveils metabolic dynamics in shake flask cultures"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4642-7336","authenticated-orcid":false,"given":"Burak","family":"Sarikaya","sequence":"first","affiliation":[{"name":"AVT \u2013 Biochemical Engineering RWTH Aachen University  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karsten","family":"G\u00fcnster","sequence":"additional","affiliation":[{"name":"AVT 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