Industrialization of bioreactors has been achieved by integrating knowledge from several applying core concepts of chemical engineering, cellular and molecular biology, and biochemistry. Mathematical modeling has provided insight into biological and physical phenomena in bioreactors. Currently, cell culture models focus on the relevant portions of the cellular activities that control the production of protein of interest. Application of existing models for improvement of bioreactor operation is first investigated. Particular attention is paid to large scale mammalian cultures for their key role in production of complex therapeutic proteins and financial success of biotechnology industry. The attributes of such culture demand enhancement in modeling as their performance is sensitive to local gradients of chemical and physical stimuli. A framework for development of dynamic and computationally feasible models that take into account the interactions of hydrodynamics and cellular activities is presented. The system is modeled as a network of zones to capture spatial heterogeneity. For computational tractability the biophase evolves dynamically over continuous time while hydrodynamics is defined over a discrete space. The discrete space consists of steady states of flow under predetermined operating conditions. Definition of states for operation through discretization of process parameters converts the problem into a dynamic transition problem. The decomposition of time and space provides the necessary formulation and modeling environment for coupling the model with nonlinear solvers and optimization of operation policy. Sensitivity of the cell culture model to operating conditions is a novel feature which allows studying the effects of hydrodynamics on growth, viability and productivity of organisms. Finally, the application of surrogate modeling for replacing the discrete space of hydrodynamics with a semi-continuous space is investigated.
Subject (authority = RUETD)
Topic
Chemical and Biochemical Engineering
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_8592
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (xi, 89 p. : ill.)
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Subject (authority = ETD-LCSH)
Topic
Bioreactors
Note (type = statement of responsibility)
by Parham Farzan
RelatedItem (type = host)
TitleInfo
Title
School of Graduate Studies Electronic Theses and Dissertations
Identifier (type = local)
rucore10001600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.