Iterative Cell Culture Bioreactor for Dynamic Density Control
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Solution Overview
Problem
Existing bioreactors lack versatility in controlling cell density and number throughout the amplification process, limiting their application in cell therapy and allowing only a narrow range of values for cell expansion.
Innovation Solution
A cell culture method and system that involves a bioreactor chamber with fluid inlet-outlet means and a pre-chamber, where cells are introduced and allowed to adhere under specific physicochemical conditions, followed by changes in these conditions to control cell adhesion and detachment, allowing for iterative adjustments to achieve target cell densities and numbers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If bioreactors use fixed culture conditions, then operational simplicity is maintained, but versatility in controlling cell density and number is limited
Solution Approach 1:
The patent implements dynamic control of culture conditions by enabling iterative adjustments of physicochemical parameters (temperature, pH, oxygen concentration, CO2 concentration) during the cell culture process. The system transitions from static to dynamic operation, allowing real-time modification of culture conditions to achieve target cell densities and numbers while maintaining operational simplicity through automated control algorithms.
Solution Approach 2:
The system employs parameter changes by modifying physicochemical conditions (temperature, pH, oxygen, CO2) to control cell adhesion and detachment. By iteratively adjusting these parameters, the system achieves versatile control over cell density and number without requiring complex mechanical modifications to the bioreactor structure.
2Productivity
If bioreactors allow multiple cell expansions, then productivity increases, but control precision over cell density decreases
Solution Approach 1:
The patent implements feedback control by continuously monitoring cell density and number during iterative expansions and adjusting culture conditions accordingly. The system uses sensor data (temperature, pH, oxygen, CO2) and cell count information to dynamically modify culture parameters, maintaining precise control even when performing multiple sequential cell expansions in the same bioreactor.
Solution Approach 2:
The system enables self-service operation by automatically performing iterative cell expansions without requiring manual intervention between cycles. The bioreactor autonomously adjusts culture conditions, performs medium exchanges, and controls cell detachment/reattachment cycles, thereby increasing productivity while maintaining control precision through integrated sensing and actuation systems.
3Adaptability or versatility
If bioreactors enable iterative cell culture steps, then adaptability improves, but operational complexity increases
Solution Approach 1:
The patent employs periodic action by implementing iterative cycles of cell culture steps (attachment, proliferation, detachment, transfer) that repeat automatically. Each cycle follows a standardized sequence of physicochemical condition modifications, allowing the system to achieve high adaptability for different cell types and expansion requirements while maintaining ease of operation through routine automated execution of periodic protocols.
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
Enables precise control over cell density and number, enhancing the versatility of bioreactors for various applications, including cell reprogramming and expansion, by modifying physicochemical conditions to manage cell adhesion and suspension, thus improving the efficiency and adaptability of cell culture processes.
Implementation Method 1
leaving the cells to settle and leaving them to stand for a predetermined time until they adhere to the at least one inner surface suitable for cell culture the physicochemical properties of which cause it to behave in such a way that it favors cell adhesion under one or several initial physicochemical conditions
Implementation Method 2
changing at least one of the initial physicochemical conditions of the culture medium to modified physicochemical conditions under which cell adhesion is prevented
Data Source
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AI summary
The invention is comprised within automated devices for cell culture. The invention relates to a cell culture method and system which allows modifying in a controlled manner the density and the number of cells in a culture. Specifically, the present invention relates to an iterative method the number of iteration steps of which is modified depending on the demand for the density and the number of cells necessary for the culture duration.