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Evaluation of single-use optical and electrochemical pH sensors in upstream bioprocessing
Culture pH is a critical process parameter during CHO cell bioreactor operations that is key for proper cell growth, protein production, and maintaining the critical quality attributes of a monoclonal antibody drug substance. The traditional means of measuring pH in bioreactors is with an electroche...
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Published in: | Heliyon 2024-02, Vol.10 (3), p.e25512-e25512, Article e25512 |
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description | Culture pH is a critical process parameter during CHO cell bioreactor operations that is key for proper cell growth, protein production, and maintaining the critical quality attributes of a monoclonal antibody drug substance. The traditional means of measuring pH in bioreactors is with an electrochemical probe that can withstand and maintain accuracy through repeated sterilization cycles. An alternative technique for measuring pH is an optical sensor composed of a fluorescent dye that is sensitive to the hydrogen ion concentration. In this work we explore single-use electrochemical and single-use optical pH sensors in stirred-tank and rocking bioreactors, respectively, to understand how their overall performance compares to traditional electrochemical probes in benchtop glass stirred tank bioreactors. We found that the single-use optical pH sensors were generally less accurate than the electrochemical probes, especially in detecting large pH drifts from the setpoint. The single-use electrochemical probes were increasingly accurate as pH was increased from |
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The traditional means of measuring pH in bioreactors is with an electrochemical probe that can withstand and maintain accuracy through repeated sterilization cycles. An alternative technique for measuring pH is an optical sensor composed of a fluorescent dye that is sensitive to the hydrogen ion concentration. In this work we explore single-use electrochemical and single-use optical pH sensors in stirred-tank and rocking bioreactors, respectively, to understand how their overall performance compares to traditional electrochemical probes in benchtop glass stirred tank bioreactors. We found that the single-use optical pH sensors were generally less accurate than the electrochemical probes, especially in detecting large pH drifts from the setpoint. The single-use electrochemical probes were increasingly accurate as pH was increased from <7.0 to 7.5 but tended to decrease in accuracy as the batch age increased. In conclusion, single-use pH sensors offer a convenient means to measure pH during an upstream bioprocess, but the limitations of these sensors should be built into process control such that deviations in process pH, and consequently potential fluctuations in product quality, can be avoided.</description><identifier>ISSN: 2405-8440</identifier><identifier>EISSN: 2405-8440</identifier><identifier>DOI: 10.1016/j.heliyon.2024.e25512</identifier><identifier>PMID: 38371965</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Biomanufacturing ; Bioprocessing ; Bioreactors ; Chinese hamster ovary cells ; CHO ; Monoclonal antibodies ; pH control ; pH sensor ; Process control ; Single-use technology</subject><ispartof>Heliyon, 2024-02, Vol.10 (3), p.e25512-e25512, Article e25512</ispartof><rights>2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c505t-5ddf37c4a3570dc95ae1b093695970c49b7cca2d6794e4ea85f5969efd94c023</citedby><cites>FETCH-LOGICAL-c505t-5ddf37c4a3570dc95ae1b093695970c49b7cca2d6794e4ea85f5969efd94c023</cites><orcidid>0000-0001-6531-5028 ; 0000-0002-9259-0540 ; 0000-0002-5568-5938 ; 0000-0002-9099-2263 ; 0000000165315028 ; 0000000255685938 ; 0000000292590540 ; 0000000290992263</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S2405844024015433$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,3549,27924,27925,45780</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38371965$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/2293626$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Fratz-Berilla, Erica J.</creatorcontrib><creatorcontrib>Kohnhorst, Casey</creatorcontrib><creatorcontrib>Trunfio, Nicholas</creatorcontrib><creatorcontrib>Bush, Xin</creatorcontrib><creatorcontrib>Gyorgypal, Aron</creatorcontrib><creatorcontrib>Agarabi, Cyrus</creatorcontrib><title>Evaluation of single-use optical and electrochemical pH sensors in upstream bioprocessing</title><title>Heliyon</title><addtitle>Heliyon</addtitle><description>Culture pH is a critical process parameter during CHO cell bioreactor operations that is key for proper cell growth, protein production, and maintaining the critical quality attributes of a monoclonal antibody drug substance. The traditional means of measuring pH in bioreactors is with an electrochemical probe that can withstand and maintain accuracy through repeated sterilization cycles. An alternative technique for measuring pH is an optical sensor composed of a fluorescent dye that is sensitive to the hydrogen ion concentration. In this work we explore single-use electrochemical and single-use optical pH sensors in stirred-tank and rocking bioreactors, respectively, to understand how their overall performance compares to traditional electrochemical probes in benchtop glass stirred tank bioreactors. We found that the single-use optical pH sensors were generally less accurate than the electrochemical probes, especially in detecting large pH drifts from the setpoint. The single-use electrochemical probes were increasingly accurate as pH was increased from <7.0 to 7.5 but tended to decrease in accuracy as the batch age increased. In conclusion, single-use pH sensors offer a convenient means to measure pH during an upstream bioprocess, but the limitations of these sensors should be built into process control such that deviations in process pH, and consequently potential fluctuations in product quality, can be avoided.</description><subject>Biomanufacturing</subject><subject>Bioprocessing</subject><subject>Bioreactors</subject><subject>Chinese hamster ovary cells</subject><subject>CHO</subject><subject>Monoclonal antibodies</subject><subject>pH control</subject><subject>pH sensor</subject><subject>Process control</subject><subject>Single-use technology</subject><issn>2405-8440</issn><issn>2405-8440</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>DOA</sourceid><recordid>eNqFUU1r3TAQFKWlCa_5CS2mp178KsuSbJ1KCWkTCPSSS09CH-s8PWTJlexA_n3k-CX0ltMuy-zszA5Cnxu8b3DDvx_3B_DuMYY9wYTugTDWkHfonFDM6p5S_P6__gxd5HzEGDes56JrP6Kztm-7RnB2jv5ePSi_qNnFUMWhyi7ce6iXDFWcZmeUr1SwFXgwc4rmAOPzbLquMoQcU65cqJYpzwnUWGkXp4KCvNJ8Qh8G5TNcnOoO3f26uru8rm___L65_HlbG4bZXDNrh7YzVLWsw9YIpqDRWLRcMNFhQ4XujFHE8k5QoKB6NjDBBQxWUINJu0M3G62N6iin5EaVHmVUTj4PYrqXKhUnHqQy2g5Ed4xpRrmmPeG9Zr3SAFz3fChcXzeumGcns3EzmIOJIRT3kpAiivAC-raBitV_C-RZji4b8F4FiEuWRJB-fXTxsENsg5oUc04wvOprsFyDlEd5ClKuQcotyLL35XRi0SPY162X2ArgxwaA8tgHB2kVC8GAdWnVaqN748QTt8CynQ</recordid><startdate>20240215</startdate><enddate>20240215</enddate><creator>Fratz-Berilla, Erica J.</creator><creator>Kohnhorst, Casey</creator><creator>Trunfio, Nicholas</creator><creator>Bush, Xin</creator><creator>Gyorgypal, Aron</creator><creator>Agarabi, Cyrus</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>OTOTI</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-6531-5028</orcidid><orcidid>https://orcid.org/0000-0002-9259-0540</orcidid><orcidid>https://orcid.org/0000-0002-5568-5938</orcidid><orcidid>https://orcid.org/0000-0002-9099-2263</orcidid><orcidid>https://orcid.org/0000000165315028</orcidid><orcidid>https://orcid.org/0000000255685938</orcidid><orcidid>https://orcid.org/0000000292590540</orcidid><orcidid>https://orcid.org/0000000290992263</orcidid></search><sort><creationdate>20240215</creationdate><title>Evaluation of single-use optical and electrochemical pH sensors in upstream bioprocessing</title><author>Fratz-Berilla, Erica J. ; Kohnhorst, Casey ; Trunfio, Nicholas ; Bush, Xin ; Gyorgypal, Aron ; Agarabi, Cyrus</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c505t-5ddf37c4a3570dc95ae1b093695970c49b7cca2d6794e4ea85f5969efd94c023</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Biomanufacturing</topic><topic>Bioprocessing</topic><topic>Bioreactors</topic><topic>Chinese hamster ovary cells</topic><topic>CHO</topic><topic>Monoclonal antibodies</topic><topic>pH control</topic><topic>pH sensor</topic><topic>Process control</topic><topic>Single-use technology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fratz-Berilla, Erica J.</creatorcontrib><creatorcontrib>Kohnhorst, Casey</creatorcontrib><creatorcontrib>Trunfio, Nicholas</creatorcontrib><creatorcontrib>Bush, Xin</creatorcontrib><creatorcontrib>Gyorgypal, Aron</creatorcontrib><creatorcontrib>Agarabi, Cyrus</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>OSTI.GOV</collection><collection>Directory of Open Access Journals</collection><jtitle>Heliyon</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fratz-Berilla, Erica J.</au><au>Kohnhorst, Casey</au><au>Trunfio, Nicholas</au><au>Bush, Xin</au><au>Gyorgypal, Aron</au><au>Agarabi, Cyrus</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluation of single-use optical and electrochemical pH sensors in upstream bioprocessing</atitle><jtitle>Heliyon</jtitle><addtitle>Heliyon</addtitle><date>2024-02-15</date><risdate>2024</risdate><volume>10</volume><issue>3</issue><spage>e25512</spage><epage>e25512</epage><pages>e25512-e25512</pages><artnum>e25512</artnum><issn>2405-8440</issn><eissn>2405-8440</eissn><abstract>Culture pH is a critical process parameter during CHO cell bioreactor operations that is key for proper cell growth, protein production, and maintaining the critical quality attributes of a monoclonal antibody drug substance. 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subjects | Biomanufacturing Bioprocessing Bioreactors Chinese hamster ovary cells CHO Monoclonal antibodies pH control pH sensor Process control Single-use technology |
title | Evaluation of single-use optical and electrochemical pH sensors in upstream bioprocessing |
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