Bioreactor Control via Nutrient Consumption Modeling
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Solution Overview
Problem
Current bioreactor systems face challenges in accurately monitoring and controlling cell growth in cell expansion processes, particularly in maintaining optimal nutrient levels and preventing contamination, while efficiently determining the volume and rate of cell growth without compromising sterility.
Innovation Solution
A bioreactor system with a membrane-separated cell expansion and nutrient supply region, utilizing in-line biosensors to monitor nutrient use and lactate levels, and adjusting pump rates and accelerations to maintain constant nutrient or lactate levels, allowing for precise control of cell growth and prediction of process completion.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If in-line biosensors are used to monitor nutrient levels continuously, then measurement precision is improved, but device complexity increases
Solution Approach 1:
The patent introduces an intermediary computational model that processes sensor data to infer cell growth parameters. Instead of directly measuring cell growth, the system uses nutrient consumption rates as an intermediary indicator, which are then processed through a computational model to derive cell population dynamics. This intermediary approach enables precise monitoring while keeping the physical sensor infrastructure relatively simple.
Solution Approach 2:
The patent replaces direct mechanical or physical cell counting methods with a computational modeling approach. By substituting complex physical measurement systems with mathematical models that process nutrient consumption data, the system achieves high measurement precision without requiring complex physical instrumentation for direct cell analysis.
2Reliability
If hermetic sampling methods are used to prevent contamination, then reliability is improved, but ease of operation deteriorates
Solution Approach 1:
The patent uses nutrient consumption rates as an intermediary parameter that can be measured without breaking sterility. Instead of directly sampling cell cultures (which risks contamination), the system measures nutrient levels in the growth medium, which provide indirect but reliable information about cell growth while maintaining the hermetic seal of the bioreactor system.
3Productivity
If pump acceleration is used to predict cell growth rate, then productivity is improved, but measurement precision requirements increase
Solution Approach 1:
The patent implements a feedback mechanism where pump acceleration measurements are continuously monitored and used to adjust nutrient delivery rates. The system measures pump acceleration, compares it against expected growth patterns, and uses this feedback to maintain optimal nutrient supply. This feedback loop enables productivity optimization while compensating for measurement uncertainties through continuous adjustment.
Solution Approach 2:
The system uses the bioreactor's own operational parameters (pump acceleration) to self-determine cell growth rates. By leveraging the existing pump infrastructure and its acceleration characteristics, the system derives productivity information without requiring separate measurement devices, thereby reducing overall measurement precision requirements while maintaining productivity assessment accuracy.
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 enables efficient and sterile monitoring of cell growth, maintaining optimal conditions for cell expansion, predicting the time for adequate cell production, and ensuring hermetic sampling without environmental contamination.
Implementation Method 1
The two regions are separated by a membrane. The membrane inhibits migration of cells from the cellular growth area to the supply area and permits migration of certain chemical compounds from the cellular growth area to the supply area
Implementation Method 2
Sensors in tubing of a bioreactor have been used to sense lactate levels as a predictor of the number of cells within the bioreactor
Implementation Method 3
providing fluid to the cellular growth area to maintain conditions conducive for cell growth
Data Source
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AI summary
A method for controlling cell expansion comprising conducting a fluid containing cellular matter into a cellular growth area; providing oxygenated fluid to said cellular growth area to maintain conditions conducive for cell growth in said cellular growth area; monitoring inflow and outflow conditions; determining rates of change (first derivative) for selected conditions and calculating cell numbers therefrom; determining a rate of change of a rate of change (second derivative) for the selected conditions and calculating a predicted process time; and terminating the growth process when adequate cell numbers have been produced and an apparatus for performing the method.