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Microfluidic Picoliter Bioreactor for Microbial Single-cell Analysis: Fabrication, System Setup, and Operation
Published on: December 7, 2013
Multi-rate nonlinear state and parameter estimation in a bioreactor
S Tatiraju1, M Soroush, R Mutharasan
1Department of Chemical Engineering, Drexel University, Philadelphia, Pennsylvania 19104, USA.
Biotechnology and Bioengineering
|April 1, 1999
Summary
This study developed a multi-rate estimator for real-time biochemical reactor monitoring. It accurately estimates cell growth and key substances using infrequent measurements, crucial for bioprocess optimization.
Area of Science:
- Biochemical Engineering
- Bioprocess Monitoring
- Cell Culture Technology
Background:
- Real-time monitoring of biochemical reactors is essential for optimizing cell culture processes.
- Hybridoma cell cultivation requires accurate estimation of various parameters for maximizing monoclonal antibody (MAb) production.
- Existing estimation methods struggle with multi-rate data and time delays inherent in bioprocesses.
Purpose of the Study:
- To design and implement a multi-rate nonlinear estimator for real-time state and parameter estimation in a pilot-scale biochemical reactor.
- To estimate critical process variables including specific growth rate, viable and total cell concentrations, glucose, glutamine, and MAb concentrations.
- To address challenges posed by infrequent and delayed measurements alongside high-frequency inferred data.
Main Methods:
- Development of a multi-rate nonlinear state and parameter estimation algorithm.
- Implementation of the estimator in a pilot-scale biochemical reactor for mouse-mouse hybridoma cell cultivation.
- Utilizing frequent dissolved oxygen concentration measurements to infer oxygen uptake rate (OUR).
- Integrating infrequent and delayed measurements of cell concentrations and key metabolites.
Main Results:
- The multi-rate estimator successfully estimated specific growth rate and concentrations of viable cells, total cells, glucose, glutamine, and MAb.
- The estimator effectively handled infrequent (2-17 h) and delayed (0.08-2.00 h) measurements.
- High-frequency OUR data (every 0.17 h) was accurately inferred and utilized for estimation.
- Performance evaluation demonstrated the efficacy of the proposed multi-rate estimation strategy.
Conclusions:
- The developed multi-rate estimator provides accurate real-time monitoring of critical parameters in biochemical reactors.
- This approach is valuable for optimizing hybridoma cell culture and MAb production.
- The method effectively overcomes limitations associated with multi-rate and delayed measurements in bioprocesses.
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