Gas Permeable Membrane for High-Density Animal Cell Transduction
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Solution Overview
Problem
Current methods for genetically modifying animal cells, particularly T cells, are inefficient in terms of the number of cells transduced and the quantity of genetic modification agents required, which can be costly and complex, and often necessitate the use of flow systems for isolating subpopulations.
Innovation Solution
The use of a gas permeable, liquid impermeable cell culture device that increases cell concentration, allowing genetic modification agents to come into closer contact with cells, thereby enhancing transduction efficiency and reducing the need for agents, while also simplifying the process by eliminating the need for flow systems through static cell culture methods.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional transduction methods are used, then cells can be genetically modified, but the transduction efficiency is low and large quantities of genetic modification agents are required
Solution Approach 1:
The patent changes the physical parameters of the cell culture system by using a gas permeable support that enables high cell concentration culture. This parameter change (from conventional low-density culture to high-density culture on gas permeable supports) directly improves transduction efficiency by increasing the proportion of cells in contact with genetic modification agents, thereby reducing the quantity of agents needed.
Solution Approach 2:
The patent uses gas permeable membranes as a copy or alternative to conventional liquid-based culture systems. The membrane provides a surface that replicates the essential function of liquid culture (supporting cell growth) while enabling high cell concentration and improved agent contact, thus achieving better transduction efficiency with fewer agents.
2Ease of operation
If flow systems are used to isolate subpopulations, then targeted cells can be selected, but the process becomes complex and costly
Solution Approach 1:
The patent extracts the essential function of cell isolation from complex flow systems and implements it through a simpler static method using gas permeable supports. By removing cells from conventional liquid culture and placing them on gas permeable membranes, the system enables straightforward isolation and transduction without requiring complex flow instrumentation.
Solution Approach 2:
The patent employs disposable gas permeable membrane supports that replace expensive, complex, and reusable flow system equipment. These simple, single-use membranes provide the necessary cell isolation and support functions at much lower cost and with greater simplicity, eliminating the need for sophisticated flow systems.
3Productivity
If high cell concentration is achieved, then transduction efficiency improves, but cell viability may decrease due to overcrowding
Solution Approach 1:
The gas permeable membrane acts as an intermediary between the cells and the culture environment. It provides mechanical support for high cell concentration while allowing gas exchange to maintain cell viability. The membrane mediates the conflict between high cell density (needed for transduction efficiency) and cell survival (needs adequate spacing and gas exchange).
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 increases the proportion of cells that can be genetically altered, reduces the quantity of genetic modification agents needed, and simplifies the process by allowing for more efficient transduction and isolation of subpopulations in a static device, potentially leading to cost savings and improved cancer therapy applications.
Implementation Method 1
a cell growth surface comprised of gas permeable, liquid impermeable material
Implementation Method 2
the entire population is removed from the device and flows past a magnetic field, whereby beads are trapped by the magnetic field
Data Source
Figure 1~2C
AI summary
This invention relates to improved methods of genetically modifying animal cells by decreasing the distance between cells and genetic modification agents in order to increase the efficiency of genetic modification and/or reduce use of gene modification agents.