Stem Cell Biomanufacturing under Uncertainty: A Case Study in Optimizing Red Blood Cell Production
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
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 manuscript proposes a rigorous computational framework for stem cell biomanufacturing under uncertainty. Our mathematical tool kit incorporates: high-fidelity modeling; single- and multivariate sensitivity analysis; global topological superstructure optimization; robust optimization. We quantitatively demonstrate 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. 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; we quantitatively evaluate the possible commercial impact of this cellular therapy using the disruptive technology paradigm.
Date Issued
2018-08-01
Date Acceptance
2017-11-13
Citation
AIChE Journal, 2018, 64 (8), pp.3011-3022
ISSN
0001-1541
Publisher
Wiley
Start Page
3011
End Page
3022
Journal / Book Title
AIChE Journal
Volume
64
Issue
8
Copyright Statement
© 2017 American Institute of Chemical Engineers. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Sponsor
Royal Academy Of Engineering
Commission of the European Communities
Engineering & Physical Science Research Council (E
Grant Number
10216/118
340719
EP/M028240/1
Subjects
Science & Technology
Technology
Engineering, Chemical
Engineering
red blood cell production
bioreactor design under uncertainty
bioprocess optimization under uncertainty
robust optimization
stem cell biomanufacturing
HOLLOW-FIBER BIOREACTOR
GLOBAL-SENSITIVITY-ANALYSIS
SUPERSTRUCTURE OPTIMIZATION
PETROLEUM FIELDS
GROWTH-MODEL
DESIGN
SYSTEMS
ROBUST
CHALLENGES
TRANSPORT
0904 Chemical Engineering
0914 Resources Engineering And Extractive Metallurgy
Chemical Engineering
Publication Status
Published
Date Publish Online
2017-11-28