Inverted Culture Well Insert for Co-culture
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Solution Overview
Problem
Current assays for screening drugs and environmental chemicals lack the ability to accurately assess metabolic competence, leading to inconsistent toxicity predictions, as they often do not simulate physiological metabolism, and existing co-culture systems face issues such as cell attachment problems and limited scalability, especially in high-throughput formats.
Innovation Solution
A culture well insert system with a planar substrate and perpendicularly extending sidewalls, allowing for the co-culturing of cells in an open-top chamber that can be inverted and inserted into a receiving culture plate, enabling improved cell adherence and media exchange, and is scalable to fit various well formats, including 96-well plates.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If permeable membrane systems are used for co-culture, then metabolic competence can be assessed, but cell attachment becomes difficult and the system becomes expensive
Solution Approach 1:
The patent removes the permeable membrane component from the co-culture system entirely. Instead of using a membrane to separate chambers, the invention uses separate culture inserts that allow media sharing without requiring permeable materials. This extraction of the problematic membrane element resolves both the cell attachment issue and the cost issue while maintaining metabolic competence assessment capability.
Solution Approach 2:
The system divides the culture well into separate compartments using non-permeable culture inserts rather than a single permeable membrane. This segmentation allows different cell types to be cultured in separate chambers that can still share media through controlled interfaces, improving cell attachment while maintaining metabolic assessment capability.
2Reliability
If permeable membrane systems are used for co-culture, then metabolic competence can be assessed, but the system becomes expensive particularly for high-throughput uses
Solution Approach 1:
The patent employs inexpensive, disposable culture inserts made from non-permeable materials that can be used in high-throughput formats. These inserts are cheaper than permeable membrane systems and are designed for single-use in 384-well and 1536-well plates, making high-throughput metabolic competence screening cost-effective.
Solution Approach 2:
The invention creates simplified copies of the co-culture system that use standard, inexpensive culture inserts rather than specialized permeable membranes. This copying approach maintains the essential functionality of metabolic competence assessment while dramatically reducing material costs for high-throughput applications.
3Measurement precision
If permeable membranes are used to divide chambers, then permeability can be measured, but the membrane inhibits cell culture from sharing media
Solution Approach 1:
The patent introduces controlled media exchange interfaces as intermediaries between culture chambers. These interfaces allow media to pass between chambers without requiring permeable membranes, enabling both media sharing and controlled permeability measurements through dedicated pathways rather than through the culture barrier itself.
Solution Approach 2:
The system separates the functions of chamber division and media exchange by using non-permeable culture inserts with dedicated media sharing interfaces. This segmentation allows the culture barrier to be impermeable (improving cell attachment) while maintaining separate controlled pathways for media exchange and permeability measurement.
4Productivity
If standard 384- or 1536-well formats are used for high-throughput screening, then productivity increases, but permeable membrane systems are not available in these formats
Solution Approach 1:
The patent designs universal culture inserts that can be adapted to multiple well formats including 96-well, 384-well, and 1536-well plates. These inserts use standard non-permeable materials and configurations that work across different plate formats, enabling high-throughput screening without being limited to specific well sizes.
Solution Approach 2:
The invention creates scaled copies of the same culture insert design for different well formats. The fundamental insert structure remains the same across 96-well, 384-well, and 1536-well configurations, allowing the system to maintain functionality while adapting to high-throughput format requirements.
Data Source
AI summary
The present invention provides improved devices for co-culture of cells. The devices include inserts having invertible wells that can be lowered into a well of any standard cell culture plate. A first population of cells can be cultured in the invertible wells of the inserts and a second population of cells can be cultured in the wells of a cell culture plate. Once the first population of cells attach to the invertible wells, the inserts are flipped over and placed into the wells of the cell culture plate to co-culture with the second population of cells.