Details
| Original language | English |
|---|---|
| Pages (from-to) | 341-351 |
| Number of pages | 11 |
| Journal | Engineering in life sciences |
| Volume | 19 |
| Issue number | 5 |
| Early online date | 4 Mar 2019 |
| Publication status | Published - 6 May 2019 |
Abstract
This study was performed in order to evaluate a new LED-based 2D-fluorescence spectrometer for in-line bioprocess monitoring of Chinese hamster ovary (CHO) cell culture processes. The new spectrometer used selected excitation wavelengths of 280, 365, and 455 nm to collect spectral data from six 10-L fed-batch processes. The technique provides data on various fluorescent compounds from the cultivation medium as well as from cell metabolism. In addition, scattered light offers information about the cultivation status. Multivariate data analysis tools were applied to analyze the large data sets of the collected fluorescence spectra. First, principal component analysis was used to accomplish an overview of all spectral data from all six CHO cultivations. Partial least square regression models were developed to correlate 2D-fluorescence spectral data with selected critical process variables as offline reference values. A separate independent fed-batch process was used for model validation and prediction. An almost continuous in-line bioprocess monitoring was realized because 2D-fluorescence spectra were collected every 10 min during the whole cultivation. The new 2D-fluorescence device demonstrates the significant potential for accurate prediction of the total cell count, viable cell count, and the cell viability. The results strongly indicated that the technique is particularly capable to distinguish between different cell statuses inside the bioreactor. In addition, spectral data provided information about the lactate metabolism shift and cellular respiration during the cultivation process. Overall, the 2D-fluorescence device is a highly sensitive tool for process analytical technology applications in mammalian cell cultures.
Keywords
- 2D-fluorescence spectroscopy, bioprocess monitoring, CHO cell cultivation, multivariate data analysis, PAT
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Biotechnology
- Environmental Science(all)
- Environmental Engineering
- Chemical Engineering(all)
- Bioengineering
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In: Engineering in life sciences, Vol. 19, No. 5, 06.05.2019, p. 341-351.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - A novel LED-based 2D-fluorescence spectroscopy system for in-line bioprocess monitoring of Chinese hamster ovary cell cultivations—Part II
AU - Claßen, Jens
AU - Graf, Alexander
AU - Aupert, Florian
AU - Solle, Dörte
AU - Höhse, Marek
AU - Scheper, Thomas
N1 - Funding information: The authors would like to thank the federal ministry of education and research for financial support.
PY - 2019/5/6
Y1 - 2019/5/6
N2 - This study was performed in order to evaluate a new LED-based 2D-fluorescence spectrometer for in-line bioprocess monitoring of Chinese hamster ovary (CHO) cell culture processes. The new spectrometer used selected excitation wavelengths of 280, 365, and 455 nm to collect spectral data from six 10-L fed-batch processes. The technique provides data on various fluorescent compounds from the cultivation medium as well as from cell metabolism. In addition, scattered light offers information about the cultivation status. Multivariate data analysis tools were applied to analyze the large data sets of the collected fluorescence spectra. First, principal component analysis was used to accomplish an overview of all spectral data from all six CHO cultivations. Partial least square regression models were developed to correlate 2D-fluorescence spectral data with selected critical process variables as offline reference values. A separate independent fed-batch process was used for model validation and prediction. An almost continuous in-line bioprocess monitoring was realized because 2D-fluorescence spectra were collected every 10 min during the whole cultivation. The new 2D-fluorescence device demonstrates the significant potential for accurate prediction of the total cell count, viable cell count, and the cell viability. The results strongly indicated that the technique is particularly capable to distinguish between different cell statuses inside the bioreactor. In addition, spectral data provided information about the lactate metabolism shift and cellular respiration during the cultivation process. Overall, the 2D-fluorescence device is a highly sensitive tool for process analytical technology applications in mammalian cell cultures.
AB - This study was performed in order to evaluate a new LED-based 2D-fluorescence spectrometer for in-line bioprocess monitoring of Chinese hamster ovary (CHO) cell culture processes. The new spectrometer used selected excitation wavelengths of 280, 365, and 455 nm to collect spectral data from six 10-L fed-batch processes. The technique provides data on various fluorescent compounds from the cultivation medium as well as from cell metabolism. In addition, scattered light offers information about the cultivation status. Multivariate data analysis tools were applied to analyze the large data sets of the collected fluorescence spectra. First, principal component analysis was used to accomplish an overview of all spectral data from all six CHO cultivations. Partial least square regression models were developed to correlate 2D-fluorescence spectral data with selected critical process variables as offline reference values. A separate independent fed-batch process was used for model validation and prediction. An almost continuous in-line bioprocess monitoring was realized because 2D-fluorescence spectra were collected every 10 min during the whole cultivation. The new 2D-fluorescence device demonstrates the significant potential for accurate prediction of the total cell count, viable cell count, and the cell viability. The results strongly indicated that the technique is particularly capable to distinguish between different cell statuses inside the bioreactor. In addition, spectral data provided information about the lactate metabolism shift and cellular respiration during the cultivation process. Overall, the 2D-fluorescence device is a highly sensitive tool for process analytical technology applications in mammalian cell cultures.
KW - 2D-fluorescence spectroscopy
KW - bioprocess monitoring
KW - CHO cell cultivation
KW - multivariate data analysis
KW - PAT
UR - http://www.scopus.com/inward/record.url?scp=85062941391&partnerID=8YFLogxK
U2 - 10.1002/elsc.201800146
DO - 10.1002/elsc.201800146
M3 - Article
AN - SCOPUS:85062941391
VL - 19
SP - 341
EP - 351
JO - Engineering in life sciences
JF - Engineering in life sciences
SN - 1618-0240
IS - 5
ER -