Passive Media Replacement in Closed Cell Expansion Systems
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Solution Overview
Problem
Cell expansion systems face challenges in maintaining optimal chemical signaling concentrations, leading to prolonged lag phases and inefficient cell growth due to dilution of chemical signaling molecules, especially in closed systems where inlet fluid flow overcompensates for evaporation, causing excessive fluid addition and resource wastage.
Innovation Solution
Implementing a passive media replacement method by interrupting protocol procedures and replacing waste bags with media bags, allowing fluid to be added at the rate of evaporation, and directly adding cytokines to the bioreactor at the sample coil to minimize dilution and degradation, thereby maintaining chemical signaling concentrations and conserving resources.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Loss of substance
If inlet fluid flow is used to compensate for evaporation in a closed cell expansion system, then fluid loss is replaced, but chemical signaling molecules are diluted and cell growth lag phase is prolonged
Solution Approach 1:
The system pre-concentrates chemical signaling molecules in a small volume reservoir (e.g., 1-10 mL) before evaporation occurs, rather than attempting to maintain concentration through continuous inlet flow. This preliminary concentration action allows the system to replace only evaporated fluid without diluting the signaling molecules, as the concentrated reservoir naturally compensates for volume loss through evaporation alone
Solution Approach 2:
The invention extracts the chemical signaling molecules from the large volume inlet fluid stream and concentrates them into a small separate reservoir. This separation allows independent control of fluid replacement (through evaporation compensation) and signaling molecule concentration (maintained in the small volume reservoir), resolving the contradiction between replacing fluid loss and preventing dilution
2Reliability
If cytokines are added to media bags for passive replacement, then chemical signaling is enhanced, but cytokines degrade quickly and require higher amounts to compensate for dilution
Solution Approach 1:
Cytokines are added to the small volume reservoir in advance, where they are protected from degradation and concentrated in a small volume. This preliminary action of adding cytokines to the concentrated reservoir rather than to large volume media bags minimizes exposure to degrading conditions and prevents dilution, maintaining signaling effectiveness while reducing total cytokine usage
Solution Approach 2:
The system creates a local concentrated environment for cytokines in the small volume reservoir, distinct from the larger system volume. This local concentration ensures high signaling effectiveness in the critical zone where cells are exposed to the factors, while minimizing total cytokine quantity needed and reducing degradation effects
3Loss of substance
If excess fluid is added to compensate for evaporation, then fluid loss is covered, but resource wastage increases and chemical signaling is diluted
Solution Approach 1:
The system uses evaporation rate as a feedback signal to control fluid replacement. By monitoring the volume loss through evaporation in the closed system, the concentrated reservoir automatically provides the exact amount of fluid replacement needed without excess addition. This feedback-based approach prevents both over-replacement (wastage) and under-replacement (fluid loss), optimizing resource efficiency
Solution Approach 2:
The concentrated reservoir serves itself by naturally compensating for evaporation through its concentrated formulation. The small volume reservoir requires no active pumping or controlled addition mechanisms - it simply maintains concentration by replacing only the evaporated portion, making the system self-regulating and eliminating resource wastage associated with active fluid management
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 reduces the lag phase of cell growth, enhances cell expansion efficiency, and significantly conserves resources by avoiding excessive fluid addition and cytokine dilution, leading to cost savings and improved cell culture outcomes.
Implementation Method 1
CCK may be small enough to pass through the microporous membrane of a hollow fiber bioreactor
Implementation Method 2
base media to be added to the system at the rate of evaporation during conditions of no active inlet fluid flow
Data Source
AI summary
Embodiments described herein generally relate to passively replacing media in a closed cell expansion system to reduce or prevent the dilution of chemical signaling used to inhibit signaling pathways that keep a cell population in the lag phase of cell growth. To prevent such dilution, active inlet fluid flow to the system may be halted. To replace fluid lost by the system, a bag containing media may be attached to the waste line in replacement of the waste or outlet bag connected thereto. By turning off one or more pumps, media from the replacement bag is added to the system at the rate of evaporation. Chemical signaling dilution may be prevented while conserving system resources. Enhancement of chemical signaling to reduce the lag phase of cell growth may further be accomplished by adding molecules, such as chemical-signaling proteins, from a direct source to the system.