Details
| Original language | English |
|---|---|
| Pages (from-to) | 2111-2121 |
| Number of pages | 11 |
| Journal | Analytical and Bioanalytical Chemistry |
| Volume | 412 |
| Issue number | 9 |
| Publication status | Published - 4 Dec 2019 |
Abstract
In a biotechnological process, standard monitored process variables are pH, partial oxygen pressure (pO2), and temperature. These process variables are important, but they do not give any information about the metabolic activity of the cell. The ISICOM is an in situ combi-sensor that is measuring the cell-specific oxygen uptake rate (qOUR) online. This variable allows a qualitative judgement of metabolic cell activity. The measuring principle of the ISICOM is based on a volume element enclosed into a small measuring chamber. Inside the measuring chamber, the pO2 and the scattered light is measured. Within a defined measuring interval, the chamber closes, and the oxygen supply for the cells is interrupted. The decreasing oxygen concentration is recorded by the pO2 optode. This measuring principle, known as the dynamic method, determines the oxygen uptake rate (OUR). Together with the scattered light signal, the cell concentration is estimated and the qOUR is available online. The design of the ISICOM is focused on functionality, sterility, long-term stability, and response time behavior so the sensor can be used in bioprocesses. With the ISICOM, measurement of online and in situ measurement of the OUR is possible. The OUR and qOUR online measurement of an animal cell batch cultivation is demonstrated, with maximum values of OUR = 2.5 mmol L−1 h−1 and a qOUR = 9.5 pmol cell−1 day−1. Information about limitation of the primary and secondary substrate is derived by the monitoring of the metabolic cell activity of bacteria and yeast cultivation processes. This sensor contributes to a higher process understanding by offering an online view on to the cell behavior. In the sense of process analytical technology (PAT), this important information is needed for bioprocesses to realize a knowledge base process control.
Keywords
- Bioprocess monitoring, Cell-specific oxygen uptake rate, OUR, Sensor
ASJC Scopus subject areas
- Chemistry(all)
- Analytical Chemistry
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry
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In: Analytical and Bioanalytical Chemistry, Vol. 412, No. 9, 04.12.2019, p. 2111-2121.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Online monitoring of the cell-specific oxygen uptake rate with an in situ combi-sensor
AU - Dahlmann, Katharina
AU - Busse, Christoph
AU - Aupert, Florian
AU - de Vries, Ingo
AU - Marquard, Daniel
AU - Solle, Dörte
AU - Lammers, Frank
AU - Scheper, Thomas
N1 - Funding information: This research was funded by the German Federal Ministry for Economic Affairs and Energy (BMWi) within the Promotion of Joint Industrial Research Program (IGF) due to a decision of the German Bundestag. It was part of the research project 19361 N by the Association for Research in Precision Mechanics, Optics, and Medical Technology (F.O.M.) under the auspices of the German Federation of Industrial Research Associations (AiF).
PY - 2019/12/4
Y1 - 2019/12/4
N2 - In a biotechnological process, standard monitored process variables are pH, partial oxygen pressure (pO2), and temperature. These process variables are important, but they do not give any information about the metabolic activity of the cell. The ISICOM is an in situ combi-sensor that is measuring the cell-specific oxygen uptake rate (qOUR) online. This variable allows a qualitative judgement of metabolic cell activity. The measuring principle of the ISICOM is based on a volume element enclosed into a small measuring chamber. Inside the measuring chamber, the pO2 and the scattered light is measured. Within a defined measuring interval, the chamber closes, and the oxygen supply for the cells is interrupted. The decreasing oxygen concentration is recorded by the pO2 optode. This measuring principle, known as the dynamic method, determines the oxygen uptake rate (OUR). Together with the scattered light signal, the cell concentration is estimated and the qOUR is available online. The design of the ISICOM is focused on functionality, sterility, long-term stability, and response time behavior so the sensor can be used in bioprocesses. With the ISICOM, measurement of online and in situ measurement of the OUR is possible. The OUR and qOUR online measurement of an animal cell batch cultivation is demonstrated, with maximum values of OUR = 2.5 mmol L−1 h−1 and a qOUR = 9.5 pmol cell−1 day−1. Information about limitation of the primary and secondary substrate is derived by the monitoring of the metabolic cell activity of bacteria and yeast cultivation processes. This sensor contributes to a higher process understanding by offering an online view on to the cell behavior. In the sense of process analytical technology (PAT), this important information is needed for bioprocesses to realize a knowledge base process control.
AB - In a biotechnological process, standard monitored process variables are pH, partial oxygen pressure (pO2), and temperature. These process variables are important, but they do not give any information about the metabolic activity of the cell. The ISICOM is an in situ combi-sensor that is measuring the cell-specific oxygen uptake rate (qOUR) online. This variable allows a qualitative judgement of metabolic cell activity. The measuring principle of the ISICOM is based on a volume element enclosed into a small measuring chamber. Inside the measuring chamber, the pO2 and the scattered light is measured. Within a defined measuring interval, the chamber closes, and the oxygen supply for the cells is interrupted. The decreasing oxygen concentration is recorded by the pO2 optode. This measuring principle, known as the dynamic method, determines the oxygen uptake rate (OUR). Together with the scattered light signal, the cell concentration is estimated and the qOUR is available online. The design of the ISICOM is focused on functionality, sterility, long-term stability, and response time behavior so the sensor can be used in bioprocesses. With the ISICOM, measurement of online and in situ measurement of the OUR is possible. The OUR and qOUR online measurement of an animal cell batch cultivation is demonstrated, with maximum values of OUR = 2.5 mmol L−1 h−1 and a qOUR = 9.5 pmol cell−1 day−1. Information about limitation of the primary and secondary substrate is derived by the monitoring of the metabolic cell activity of bacteria and yeast cultivation processes. This sensor contributes to a higher process understanding by offering an online view on to the cell behavior. In the sense of process analytical technology (PAT), this important information is needed for bioprocesses to realize a knowledge base process control.
KW - Bioprocess monitoring
KW - Cell-specific oxygen uptake rate
KW - OUR
KW - Sensor
UR - http://www.scopus.com/inward/record.url?scp=85076096719&partnerID=8YFLogxK
U2 - 10.1007/s00216-019-02260-9
DO - 10.1007/s00216-019-02260-9
M3 - Article
C2 - 31802179
AN - SCOPUS:85076096719
VL - 412
SP - 2111
EP - 2121
JO - Analytical and Bioanalytical Chemistry
JF - Analytical and Bioanalytical Chemistry
SN - 1618-2642
IS - 9
ER -