Model-based cell number quantification using online single-oxygen sensor data for tissue engineering perfusion bioreactors.
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 × 10(5) cells to potentially multiple millions of cells, and can open-up new possibilities for effective bioprocess monitoring.
Division M3-BIORES: Measure, Model & Manage Bioresponses, KU Leuven, Heverlee, Belgium; Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Leuven, Belgium.
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T
Lambrechts
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Papantoniou
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M
Sonnaert
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J
Schrooten
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JM
Aerts
D019149:Bioreactors; D015374:Biosensing Techniques / Q000295:instrumentation*; D002452:Cell Count; D018929:Cell Culture Techniques / Q000295:instrumentation; D002478:Cells, Cultured; D004867:Equipment Design; D006801:Humans; D008954:Models, Biological; D010100:Oxygen / Q000032:analysis* / Q000378:metabolism*; D010477:Perfusion / Q000295:instrumentation; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D023822:Tissue Engineering / Q000295:instrumentation*; D054457:Tissue Scaffolds / Q000737:chemistry
D010100:Oxygen
bioprocess control; data-based mechanistic modeling; online monitoring; oxygen sensor; stem cell bioreactor; tissue engineering