Model‐based cell number quantification using online single‐oxygen sensor data for tissue engineering perfusion bioreactors

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Abstract
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 (R2 = 0.80) and the metabolic activity of the cells (R2 = 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 × 105 cells to potentially multiple millions of cells, and can open‐up new possibilities for effective bioprocess monitoring. Biotechnol. Bioeng. 2014;111: 1982–1992.
Funding Information
  • 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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