Journal
BIOTECHNOLOGY AND BIOENGINEERING
Volume 111, Issue 10, Pages 1982-1992Publisher
WILEY
DOI: 10.1002/bit.25274
Keywords
bioprocess control; oxygen sensor; tissue engineering; stem cell bioreactor; online monitoring; data-based mechanistic modeling
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Funding
- KU Leuven Concerted Research Actions [GOA/13/016]
- Agency for Innovation by Science and Technology [IWT/111457]
- Research Foundation Flanders (FWO Vlaanderen)
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Online and non-invasive quantification of critical tissue engineering (TE) construct quality attributes in TE bioreactors is indispensable for the cost-effective up-scaling and automation of cellular construct manufacturing. However, appropriate monitoring techniques for cellular constructs in bioreactors are still lacking. This study presents a generic and robust approach to determine cell number and metabolic activity of cell-based TE constructs in perfusion bioreactors based on single oxygen sensor data in dynamic perfusion conditions. A data-based mechanistic modeling technique was used that is able to correlate the number of cells within the scaffold (R-2 = 0.80) and the metabolic activity of the cells (R-2 = 0.82) to the dynamics of the oxygen response to step changes in the perfusion rate. This generic non-destructive measurement technique is effective for a large range of cells, from as low as 1.0 x 10(5) cells to potentially multiple millions of cells, and can open-up new possibilities for effective bioprocess monitoring. (C) 2014 Wiley Periodicals, Inc.
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