Dynamic Temperature Control for Eukaryotic Cell Cultures
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Solution Overview
Problem
Eukaryotic cell cultures are sensitive to variations in growth conditions, leading to inconsistencies in protein production, making it challenging for pharmaceutical companies to maintain reproducibility and efficiency in bioreactor processes.
Innovation Solution
A method and system for dynamically controlling the temperature of eukaryotic cell cultures by predicting cell density and adjusting it within a narrow range (0.1-1°C) to maintain target cell densities and product quality, compensating for initial variations and system failures.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If temperature is kept constant throughout the growth phase and stationary phase, then reproducibility and product quality consistency are improved, but the ability to compensate for initial variations and system failures is reduced
Solution Approach 1:
The patent applies dynamics by transitioning from static temperature control to dynamic temperature adjustment. The control system continuously monitors cell density and automatically adjusts temperature within narrow ranges (0.1-1°C) based on real-time measurements, allowing the system to adapt to variations while maintaining reproducibility.
Solution Approach 2:
The patent implements feedback control by measuring cell density at multiple time points and using this information to adjust temperature setpoints. The control logic compares predicted cell density with target values and modifies temperature accordingly, creating a closed-loop system that compensates for deviations while maintaining consistent product quality.
2Adaptability or versatility
If temperature adjustments are made to compensate for variations, then adaptability and compensation capability are improved, but temperature stability and potential impact on cell metabolism are worsened
Solution Approach 1:
The patent applies partial action by making small, incremental temperature adjustments within narrow ranges (0.1-1°C) rather than large deviations. This limited scope of adjustment allows compensation for variations while minimizing impact on cell metabolism and maintaining temperature stability.
Solution Approach 2:
The patent changes the temperature parameter dynamically based on measured cell density and predicted outcomes. By adjusting temperature within physiologically tolerable limits and using prediction models to guide adjustments, the system achieves adaptability without compromising temperature stability or cellular metabolic processes.
3Productivity
If dynamic temperature control is implemented, then productivity and production time are improved, but device complexity and control system requirements are worsened
Solution Approach 1:
The patent applies self-service by implementing an automated control system that monitors cell density and adjusts temperature without manual intervention. The control logic autonomously processes measurements, predicts cell density, and executes temperature adjustments, reducing productivity losses while managing complexity through automation.
Solution Approach 2:
The patent replaces manual temperature adjustment mechanisms with an automated control system that uses sensors, prediction algorithms, and automated actuators. This substitution reduces the operational burden and improves productivity while managing complexity through electronic and computational systems rather than mechanical procedures.
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 approach allows for precise control of cell growth, reducing production time by up to 20% and ensuring consistent bio-product quality, even with deviations in initial conditions or system failures, by maintaining temperature adjustments within physiologically tolerable limits.
Implementation Method 1
adjusting the temperature of the culture medium in the first tank if the predicted cell density deviates from the target cell density. The adjustment is performed either by increasing the temperature by 0.1 °C to 1°C if the predicted cell density is lower than the target cell density; or by decreasing the temperature by 0.1 °C to 1°C if the predicted cell density is higher than the target cell density
Data Source
Figure 1
Figure 2a~2c
Figure 2d~3
AI summary
The invention relates to a system (100) for controlling the growth of eukaryotic cells. The system comprises a control logic (116) and a processor (104) configured for executing the control logic. The control logic is operatively coupled to a first tank (130) comprising eukaryotic cells in a culture medium (M1). The control logic is configured for: - receiving a target cell density (114) and a target time (112); for each of a plurality of time intervals: • receiving a measured cell density (122) of the eukaryotic cells in the culture medium of the first tank; computing a predicted cell density at target time as a function of at least the measured cell density; • comparing the predicted cell density and the target cell density; • adjusting, by the control logic, the temperature of the culture medium in the first tank if the predicted cell density deviates from the target cell density by increasing the temperature by 0.1 °C to 1°C if the predicted cell density is lower than the target cell density; or by decreasing the temperature by 0.1 °C to 1°C if the predicted cell density is higher than the target cell density.