Modeling and optimization of bioreactors and lipid bodies

Meyer, Danielle

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https://hdl.handle.net/2142/127233 Copy

Description

Title

Modeling and optimization of bioreactors and lipid bodies

Author(s)

Meyer, Danielle

Issue Date

2024-12-04

Director of Research (if dissertation) or Advisor (if thesis)

Rao, Christopher V

Doctoral Committee Chair(s)

Rao, Christopher V

Committee Member(s)

• Kraft, Mary L
• Jin, Yong-Su
• Shukla, Diwakar

Department of Study

Chemical & Biomolecular Engr

Discipline

Chemical Engineering

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• bioreactor
• scaling
• mass transfer efficiency
• lipid bodies
• yarrowia lipolytica

Abstract

Bioprocesses are highly promising - both as replacements for traditional chemical manufacturing techniques as well as for entirely novel products. However, they are currently highly limited by repeated failures to successfully transition from benchtop reactions to the industrial scales required, with limited successes primarily being driven by high priced specialty products where commercial success is not predicated on scaling efficiency increases. Resultingly, this leaves a major gap in commercial viability which often leads to costly failures. In this dissertation, I will present my work on mass transport modeling in biological systems in computational as well as experimental methods. First, both reactor configuration and starting conditions are optimized for aerobic fermentation of methane in airlift fermenters using Methylococcus capsulatus were optimized to validate simulation methods. While initial reactor design and construction were limited by physical space constraints, with experimental growth data, Lattice-Boltzmann based simulation approaches entirely removed this limitation while increasing design iteration throughput. Using the MSTAR CFD solver and modeled reaction kinetics and growth dynamics, experimental performance was replicated and the specific effects of individual design choices were measured for performance improvements for methane capture efficiency against volumetric throughput. While increasing column height continuously increased gas dissolution mass transport efficiency, the inclusion of settling zones was determined to have no positive impact though their placement could detrimentally affect overall reactor performance and entrainment. Second, the relationships of various factors including mixing speed, relative gas sparging rate, aspect ratio, and overall reactor volume against mass transfer efficiency were compared and a predictive model was developed to predict reactor mass transfer efficiency across multiple orders of magnitude using an initial design starting point while minimizing error. Toward this end, the effects of solutions to mixing inefficiencies were also measured and incorporated to address mass transfer efficiency losses. Over the course of this process, the development of localized lower mixing zones was also studied and specific regions within reactor volumes identified. Because of their highly nonlinear growth across multiple volume order increases, these regions had outsized effects on mass transfer predictability and addressing them became a key component to minimizing model error. The final version was able to predict reactor mass transfer efficiency to within 2.5% across a 125-fold volume change in a corner case of the search space while fitted to mass transfer data across a range of only 4-fold. Finally, the relationship of lipid body growth dynamics and lipid accumulation within Yarrowia lipolytica was studied to measure effects of different growth regimes on lipid body physiology and accumulation. In this research, using lipid body imaging with BODIPY staining and automated measurements by machine learning, lipid body size distributions at multiple growth phases between initial growth and oleaginous were measured as well as across carbon to nitrogen ratios ranging from 5 to 80 to measure the effects of excess carbon on individual lipid bodies and their size distributions.

Graduation Semester

2024-12

Type of Resource

Thesis

Handle URL

https://hdl.handle.net/2142/127233

Copyright and License Information

Copyright 2024 Danielle Meyer

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