Cell Growth Control Through Biomass Capacitance Temperature Feedback
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Solution Overview
Problem
Existing bioreactor processes struggle with precise control of cell growth due to exponential growth characteristics and small perturbations in process conditions, leading to difficulties in timing cell density-based decisions such as temperature shifting, and offline measurement techniques fail to capture critical data like exact cell peak time and density.
Innovation Solution
Implementing a biomass capacitance probe to measure viable cell density and using a temperature control loop to adjust the growth rate of cells, with a pre-determined growth curve and bolus feeds to modulate reactor temperature.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If standard offline measurement techniques are used to monitor cell density, then the measurement process is simple, but the exact cell peak time and density cannot be captured
Solution Approach 1:
The patent replaces mechanical/manual offline sampling and measurement with an optical measurement system that continuously monitors cell density in real-time, enabling precise capture of cell peak time and density without manual intervention
Solution Approach 2:
The patent implements continuous real-time monitoring of cell density throughout the culture process, replacing discrete offline measurements with uninterrupted data collection that captures the exact moment of cell peak and provides continuous feedback for process control
2Manufacturing precision
If temperature is held constant during cell culture, then the process is simple to control, but the timing of cell growth from inoculation to peak cannot be precisely controlled
Solution Approach 1:
The patent transitions from static constant temperature cultivation to dynamic temperature control, where temperature is continuously adjusted based on real-time cell density feedback to precisely control the timing of cell growth phases
Solution Approach 2:
The patent implements a closed-loop feedback system where real-time cell density measurements are continuously fed back to the temperature control system, which automatically adjusts temperature to achieve precise control over cell growth timing and peak density
3Reliability
If small perturbations in process conditions occur, then the process is easier to operate, but large impacts on cell density and process performance result due to exponential growth
Solution Approach 1:
The patent implements real-time feedback monitoring of cell density with automatic control adjustments that compensate for perturbations in process conditions, preventing small variations from amplifying during exponential growth and ensuring stable process performance
Solution Approach 2:
The patent uses real-time monitoring and predictive control to anticipate and compensate for potential deviations during exponential growth, applying corrective temperature adjustments before small perturbations can lead to large impacts on cell density and process performance
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 allows for precise control of cell growth, minimizing fluctuations and enabling accurate timing of cell peak density, thereby enhancing process efficiency and productivity.
Implementation Method 1
measuring the viable cell density of the cells growing in culture using a biomass capacitance probe
Implementation Method 2
utilizing a temperature control loop to modulate the reactor temperature and adjust the growth rate of the cells
Data Source
AI summary
The present invention relates to the use of online biomass capacitance monitoring in cultures as a way to control the growth of cells through the use of a temperature control loop. In certain embodiments, a biomass capacitance probe is used to measure the cell density, and a predetermined growth curve is used to adjust the temperature in the culture.