Proton-transfer-reaction mass spectrometry (PTR-MS) for online monitoring of glucose depletion and cell concentrations in HEK 293 gene therapy processes
Objectives The applicability of proton-transfer-reaction mass spectrometry (PTR-MS) as a versatile online monitoring tool to increase consistency and robustness for recombinant adeno-associated virus (rAAV) producing HEK 293 bioprocesses was evaluated. We present a structured workflow to extract pro...
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| Published in: | Biotechnology letters Vol. 44; no. 1; pp. 77 - 88 |
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| Main Authors: | , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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Dordrecht
Springer Netherlands
01-01-2022
Springer Nature B.V |
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| Abstract | Objectives
The applicability of proton-transfer-reaction mass spectrometry (PTR-MS) as a versatile online monitoring tool to increase consistency and robustness for recombinant adeno-associated virus (rAAV) producing HEK 293 bioprocesses was evaluated. We present a structured workflow to extract process relevant information from PTR-MS data.
Results
Reproducibility of volatile organic compound (VOC) measurements was demonstrated with spiking experiments and the process data sets used for applicability evaluation consisted of HEK 293 cell culture triplicates with and without transfection. The developed data workflow enabled the identification of six VOCs, of which two were used to develop a soft sensor providing better real-time estimates than the conventional capacitance sensor. Acetaldehyde, another VOC, provides online process information about glucose depletion that can directly be used for process control purposes.
Conclusions
The potential of PTR-MS for HEK 293 cell culture monitoring has been shown. VOC data derived information can be used to develop soft sensors and to directly set up new process control strategies. |
|---|---|
| AbstractList | Objectives
The applicability of proton-transfer-reaction mass spectrometry (PTR-MS) as a versatile online monitoring tool to increase consistency and robustness for recombinant adeno-associated virus (rAAV) producing HEK 293 bioprocesses was evaluated. We present a structured workflow to extract process relevant information from PTR-MS data.
Results
Reproducibility of volatile organic compound (VOC) measurements was demonstrated with spiking experiments and the process data sets used for applicability evaluation consisted of HEK 293 cell culture triplicates with and without transfection. The developed data workflow enabled the identification of six VOCs, of which two were used to develop a soft sensor providing better real-time estimates than the conventional capacitance sensor. Acetaldehyde, another VOC, provides online process information about glucose depletion that can directly be used for process control purposes.
Conclusions
The potential of PTR-MS for HEK 293 cell culture monitoring has been shown. VOC data derived information can be used to develop soft sensors and to directly set up new process control strategies. OBJECTIVESThe applicability of proton-transfer-reaction mass spectrometry (PTR-MS) as a versatile online monitoring tool to increase consistency and robustness for recombinant adeno-associated virus (rAAV) producing HEK 293 bioprocesses was evaluated. We present a structured workflow to extract process relevant information from PTR-MS data. RESULTSReproducibility of volatile organic compound (VOC) measurements was demonstrated with spiking experiments and the process data sets used for applicability evaluation consisted of HEK 293 cell culture triplicates with and without transfection. The developed data workflow enabled the identification of six VOCs, of which two were used to develop a soft sensor providing better real-time estimates than the conventional capacitance sensor. Acetaldehyde, another VOC, provides online process information about glucose depletion that can directly be used for process control purposes. CONCLUSIONSThe potential of PTR-MS for HEK 293 cell culture monitoring has been shown. VOC data derived information can be used to develop soft sensors and to directly set up new process control strategies. Abstract Objectives The applicability of proton-transfer-reaction mass spectrometry (PTR-MS) as a versatile online monitoring tool to increase consistency and robustness for recombinant adeno-associated virus (rAAV) producing HEK 293 bioprocesses was evaluated. We present a structured workflow to extract process relevant information from PTR-MS data. Results Reproducibility of volatile organic compound (VOC) measurements was demonstrated with spiking experiments and the process data sets used for applicability evaluation consisted of HEK 293 cell culture triplicates with and without transfection. The developed data workflow enabled the identification of six VOCs, of which two were used to develop a soft sensor providing better real-time estimates than the conventional capacitance sensor. Acetaldehyde, another VOC, provides online process information about glucose depletion that can directly be used for process control purposes. Conclusions The potential of PTR-MS for HEK 293 cell culture monitoring has been shown. VOC data derived information can be used to develop soft sensors and to directly set up new process control strategies. The applicability of proton-transfer-reaction mass spectrometry (PTR-MS) as a versatile online monitoring tool to increase consistency and robustness for recombinant adeno-associated virus (rAAV) producing HEK 293 bioprocesses was evaluated. We present a structured workflow to extract process relevant information from PTR-MS data. Reproducibility of volatile organic compound (VOC) measurements was demonstrated with spiking experiments and the process data sets used for applicability evaluation consisted of HEK 293 cell culture triplicates with and without transfection. The developed data workflow enabled the identification of six VOCs, of which two were used to develop a soft sensor providing better real-time estimates than the conventional capacitance sensor. Acetaldehyde, another VOC, provides online process information about glucose depletion that can directly be used for process control purposes. The potential of PTR-MS for HEK 293 cell culture monitoring has been shown. VOC data derived information can be used to develop soft sensors and to directly set up new process control strategies. |
| Author | Maccani, Andreas Kraus, Barbara Kapeller, Ewald Striedner, Gerald Bayer, Benjamin Hernandez Bort, Juan A. Jahn, Johanna Duerkop, Mark Pletzenauer, Robert |
| Author_xml | – sequence: 1 givenname: Benjamin surname: Bayer fullname: Bayer, Benjamin organization: Novasign GmbH, University of Natural Resources and Life Sciences – sequence: 2 givenname: Andreas surname: Maccani fullname: Maccani, Andreas organization: Gene Therapy Process Development, Baxalta Innovations GmbH, a Part of Takeda Companies – sequence: 3 givenname: Johanna surname: Jahn fullname: Jahn, Johanna organization: Gene Therapy Process Development, Baxalta Innovations GmbH, a Part of Takeda Companies – sequence: 4 givenname: Mark surname: Duerkop fullname: Duerkop, Mark organization: Novasign GmbH, University of Natural Resources and Life Sciences – sequence: 5 givenname: Ewald surname: Kapeller fullname: Kapeller, Ewald organization: Gene Therapy Process Development, Baxalta Innovations GmbH, a Part of Takeda Companies – sequence: 6 givenname: Robert surname: Pletzenauer fullname: Pletzenauer, Robert organization: Gene Therapy Process Development, Baxalta Innovations GmbH, a Part of Takeda Companies – sequence: 7 givenname: Barbara surname: Kraus fullname: Kraus, Barbara organization: Gene Therapy Process Development, Baxalta Innovations GmbH, a Part of Takeda Companies – sequence: 8 givenname: Gerald surname: Striedner fullname: Striedner, Gerald organization: Novasign GmbH, University of Natural Resources and Life Sciences – sequence: 9 givenname: Juan A. orcidid: 0000-0003-2348-4864 surname: Hernandez Bort fullname: Hernandez Bort, Juan A. email: juan.hernandezbort@takeda.com organization: Gene Therapy Process Development, Baxalta Innovations GmbH, a Part of Takeda Companies |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/34767126$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_3389_fceng_2022_1044245 crossref_primary_10_1002_biot_202200381 |
| Cites_doi | 10.1016/0168-1176(95)04294-U 10.1002/elsc.201900076 10.1016/j.jviromet.2013.10.038 10.1038/mt.2015.187 10.1007/s00216-010-3781-x 10.1002/bit.27532 10.1002/btpr.1853 10.1002/biot.201900551 10.1002/bit.24579 10.1128/AEM.02069-07 10.1038/d41573-021-00017-7 10.1016/j.omtm.2020.06.004 10.1002/bit.26383 10.1007/s40259-017-0234-5 10.1016/j.tibtech.2014.03.008 10.1214/aos/1176345638 10.1088/1752-7163/ab3d23 10.1016/S0169-7439(97)00032-4 10.1016/j.omtm.2018.11.004 |
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| Keywords | PTR-MS monitoring HEK 293 cell culture monitoring rAAV process Glucose online monitoring Cell culture PAT Biomass soft sensor |
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The applicability of proton-transfer-reaction mass spectrometry (PTR-MS) as a versatile online monitoring tool to increase consistency and... The applicability of proton-transfer-reaction mass spectrometry (PTR-MS) as a versatile online monitoring tool to increase consistency and robustness for... Abstract Objectives The applicability of proton-transfer-reaction mass spectrometry (PTR-MS) as a versatile online monitoring tool to increase consistency and... ObjectivesThe applicability of proton-transfer-reaction mass spectrometry (PTR-MS) as a versatile online monitoring tool to increase consistency and robustness... OBJECTIVESThe applicability of proton-transfer-reaction mass spectrometry (PTR-MS) as a versatile online monitoring tool to increase consistency and robustness... |
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| SubjectTerms | Acetaldehyde Applied Microbiology Biochemistry Biomedical and Life Sciences Biotechnology Capacitance Cell culture Depletion Evaluation Gene therapy Genetic Therapy Glucose HEK293 Cells Humans Information processing Life Sciences Mass spectrometry Mass Spectrometry - methods Mass spectroscopy Microbiology Monitoring Organic compounds Original Research Paper Process control Process controls Protons Reproducibility of Results Scientific imaging Spectroscopy Transfection VOCs Volatile organic compounds Volatile Organic Compounds - analysis Workflow |
| Title | Proton-transfer-reaction mass spectrometry (PTR-MS) for online monitoring of glucose depletion and cell concentrations in HEK 293 gene therapy processes |
| URI | https://link.springer.com/article/10.1007/s10529-021-03205-y https://www.ncbi.nlm.nih.gov/pubmed/34767126 https://www.proquest.com/docview/2629521845 https://search.proquest.com/docview/2597487832 https://pubmed.ncbi.nlm.nih.gov/PMC8854141 |
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