Stem cell biomanufacturing under uncertainty: A case study in optimizing red blood cell production Academic Article uri icon


  • As breakthrough cellular therapy discoveries are translated into reliable, commercializable applications, effective stem cell biomanufacturing requires systematically developing and optimizing bioprocess design and operation. This article proposes a rigorous computational framework for stem cell biomanufacturing under uncertainty. Our mathematical tool kit incorporates: high-fidelity modeling, single variate and multivariate sensitivity analysis, global topological superstructure optimization, and robust optimization. The advantages of the proposed bioprocess optimization framework using, as a case study, a dual hollow fiber bioreactor producing red blood cells from progenitor cells were quantitatively demonstrated. The optimization phase reduces the cost by a factor of 4, and the price of insuring process performance against uncertainty is approximately 15% over the nominal optimal solution. Mathematical modeling and optimization can guide decision making; the possible commercial impact of this cellular therapy using the disruptive technology paradigm was quantitatively evaluated.

altmetric score

  • 4.7

author list (cited authors)

  • Misener, R., Allenby, M. C., Fuentes‐Garí, M., Gupta, K., Wiggins, T., Panoskaltsis, N., Pistikopoulos, E. N., & Mantalaris, A.

citation count

  • 4

publication date

  • December 2017