Optical Sensor Bioreactor Perfusion Control
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Solution Overview
Problem
Current methods for monitoring cell growth and regulating perfusion rates in bioreactors compromise sterility and are not suitable for flexible cellbags, as they require sampling and are large and expensive, posing contamination risks and integration challenges.
Innovation Solution
An inverse linear relationship between dissolved oxygen concentrations and cell density is utilized to predict cell concentration, allowing for the regulation of perfusion rates based on oxygen uptake measurements without sampling, using an embedded optical sensor to continuously monitor and control media perfusion rates in a bioreactor.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If optical probes or in situ microscopes are used to monitor cell growth, then measurement precision is improved, but device complexity and cost increase, and sterility is compromised
Solution Approach 1:
The patent replaces complex mechanical probe systems with a simplified optical absorption measurement system. Instead of using FBRM probes, PVM systems, or in situ microscopes that require physical immersion into the culture, the invention uses standard optical sensors to measure light absorption at specific wavelengths (e.g., 600 nm) to determine cell density. This substitution maintains measurement capability while eliminating the complexity and sterility issues of probe-based systems.
2Measurement precision
If manual sampling is performed to monitor cell growth, then measurement precision is improved, but sterility is compromised due to exposure to external environment
Solution Approach 1:
The patent introduces an intermediary measurement approach by using optical absorption measurements through the bioreactor wall or integrated optical sensors. This intermediary method allows cell density monitoring without direct contact between the external environment and the cell culture, thereby eliminating contamination risk while maintaining measurement precision. The optical measurements serve as a mediator that bridges the need for monitoring with the requirement for sterility.
3Measurement precision
If large expensive inline cell counters are integrated into bioreactors, then measurement precision is improved, but adaptability to flexible cellbags deteriorates
Solution Approach 1:
The patent changes the measurement parameters from complex probe-based physical measurements to simple optical absorption measurements at specific wavelengths. This parameter change allows the use of standard optical sensors that can be easily integrated into flexible cellbags without requiring the rigid, large-scale infrastructure of traditional inline cell counters. The measurement is performed by passing light through the bioreactor wall or using embedded optical fibers, making the system adaptable to flexible configurations.
4Productivity
If dissolved oxygen readings are used to determine agitation rate, then productivity is improved, but reliability deteriorates for sensitive primary cells
Solution Approach 1:
The patent implements a feedback control system that uses optical absorption measurements to monitor cell density and automatically adjusts media perfusion rates accordingly. The system continuously measures cell density and provides feedback to the control algorithm, which adjusts the perfusion rate to maintain optimal growth conditions. This feedback mechanism ensures reliable cell viability by preventing over-perfusion while maximizing productivity through automated adjustment based on real-time cell density data.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This method enables accurate prediction of cell density and automation of perfusion rates, reducing human error and maintaining sterility, making it suitable for sensitive cells like T-cells in flexible bioreactors, while eliminating the need for manual sampling and large, expensive equipment.
Implementation Method 1
Optical probes which measure the pH and level of dissolved oxygen (DO) in a bioreactor culture are available
Implementation Method 2
an inverse linear relationship exists between dissolved oxygen concentrations and cell density for primary cells cultured in suspension culture. As the number of cell increases, the concentration of dissolved oxygen decreases
Data Source
AI summary
The present invention relates to cell culture in bioreactors, such as flexible cellbag bioreactors. More closely the invention relates to a method and system for determining the cell density in a bioreactor culture and for controlling the perfusion rate of a suspension culture of cells in a bioreactor, comprising measuring the oxygen uptake of primary mononuclear cells in a non-static bioreactor.