TY  - JOUR
U1  - Zeitschriftenartikel, wissenschaftlich - begutachtet (reviewed)
A1  - Drieschner, Tobias
A1  - Ostertag, Edwin
A1  - Boldrini, Barbara
A1  - Lorenz, Anita
A1  - Brecht, Marc
A1  - Rebner, Karsten
T1  - Direct optical detection of cell density and viability of mammalian cells by means of UV/VIS spectroscopy
JF  - Analytical and bioanalytical chemistry : a merger of Fresenius' journal of analytical chemistry and Analusis
N2  - The critical process parameters cell density and viability during mammalian cell cultivation are assessed by UV/VIS spectroscopy in combination with multivariate data analytical methods. This direct optical detection technique uses a commercial optical probe to acquire spectra in a label-free way without signal enhancement. For the cultivation, an inverse cultivation protocol is applied, which simulates the exponential growth phase by exponentially replacing cells and metabolites of a growing Chinese hamster ovary cell batch with fresh medium. For the simulation of the death phase, a batch of growing cells is progressively replaced by a batch with completely starved cells. Thus, the most important parts of an industrial batch cultivation are easily imitated. The cell viability was determined by the well-established method partial least squares regression (PLS). To further improve process knowledge, the viability has been determined from the spectra based on a multivariate curve resolution (MCR) model. With this approach, the progress of the cultivations can be continuously monitored solely based on an UV/VIS sensor. Thus, the monitoring of critical process parameters is possible inline within a mammalian cell cultivation process, especially the viable cell density. In addition, the beginning of cell death can be detected by this method which allows us to determine the cell viability with acceptable error. The combination of inline UV/VIS spectroscopy with multivariate curve resolution generates additional process knowledge complementary to PLS and is considered a suitable process analytical tool for monitoring industrial cultivation processes.
KW  - multivariate curve resolution
KW  - UV/VIS spectroscopy
KW  - partial least squares regression
KW  - cell viability
KW  - process analytical technology
Y1  - 2020
SN  - 1618-2642
SS  - 1618-2642
U6  - https://doi.org/10.1007/s00216-019-02322-y
DO  - https://doi.org/10.1007/s00216-019-02322-y
VL  - 412
IS  - 14
SP  - 3359
EP  - 3371
S1  - 13
PB  - Springer
CY  - Berlin ; Heidelberg
ER  -