Biocapacitance Sensors for In-Line Viable Cell Density Monitoring in Complex Bioreactors

The precise monitoring of Viable Cell Density (VCD) in bioreactors is crucial for optimizing bioprocesses, improving yield, and maintaining product quality. VCD can be effectively indicated by biocapacitance, a capacitance associated with the viable cell membrane, which can be detected through Impedance/Dielectric Spectroscopy (IS/DS) The advancements of high-performance computing and Artificial Intelligence (AI) in recent decades have expedited the measuring and analysis of IS/DS enabling real-time monitoring of biocapacitance. In-line biocapacitance sensors has been widely applied for VCD monitoring in lab-scale adherent cell cultures and in high-throughput suspension cell cultures. However, this promising technology has not been effectively applied to high-throughput adherent cell cultures and lab-scale suspension cell cultures due to the complexity of the bioreactors. The Hollow Fiber Bioreactor (HFBR) is a high-efficiency bioreactor for high-throughput adherent cell culture thanks to its high surface-to-volume ratio. However, the packed interior of the HFBR presents unique challenges in achieving in-line biocapacitance sensing. This dissertation presents the development and characterization of biocapacitance sensors tailored for HFBRs. The study encompasses theoretical analysis, modeling, design, fabrication, and data analysis to create and optimize these sensors. The technology developed in this study is the first to achieve direct in-line VCD monitoring for high-throughput adherent cell culture. Key findings demonstrate that the sensors exhibit high sensitivity and potential to achieve spatial resolution, effectively monitoring VCD in real-time. Comprehensive data analysis and theoretical insights provides deeper understanding and optimization of sensor performance. Additionally, the work includes the development and assessment of two other biocapacitance sensors for lab-scale suspension cell cultures, which are also insufficiently addressed in current market and research. This work highlights the critical role of sensor technology, theoretical analysis, and data processing in advancing bioreactor systems.

Level thesis:degree_level

Doctoral

Department dc:contributor.department

Materials Science and Engineering

Grantor dc:publisher

Georgia Institute of Technology

Year dc:date.issued

2024

Author dc:creator

• Liu, Zhaonan

Advisors dc:contributor.advisor

• Zhang, Chuck
• Wang, Ben

Committee members dc:contributor.committeemember

• Gerhardt, Rosario
• Yao, Donggang
• Wang, Kan

• Impedance spectroscopy
• Biocapacitance
• Viable cell density
• Hollow fiber bioreactor

Language dc:language.iso

en_US

Handle dc:identifier.uri

https://hdl.handle.net/1853/80050

OAI identifier oai:identifier

oai:repository.gatech.edu:1853/80050