Dynamic Temperature Control for Eukaryotic Cell Cultures

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

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

VSEngineering 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

Engineering Contradiction:
ImprovereproducibilityVSAvoidcompensation capability
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

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.

Inventive Principle:
Principle #15Dynamics

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.

Inventive Principle:
Principle #23Feedback

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

Engineering Contradiction:
Improvecompensation capabilityVSAvoidtemperature stability
Core Design Contradiction:
Adaptability or versatilityVSStability of the object's composition

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.

Inventive Principle:
Principle #16Partial or excessive action

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.

Inventive Principle:
Principle #35Parameter changes

3Productivity

If dynamic temperature control is implemented, then productivity and production time are improved, but device complexity and control system requirements are worsened

Engineering Contradiction:
Improveproduction timeVSAvoidcontrol system complexity
Core Design Contradiction:
ProductivityVSDevice complexity

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.

Inventive Principle:
Principle #25Self-service

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.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

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

Methodology Applied
Scientific EffectTemperature adjustment: Heating

Data Source

PatentEP3559203B1Growth control of eukaryotic cells
Publication Date: 2020.12.02 F HOFFMANN LA ROCHE & CO AG
  • EP3559203B1 patent drawingFigure 1
  • EP3559203B1 patent drawingFigure 2a~2c
  • EP3559203B1 patent drawingFigure 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.