Microwell Cell Carrier Structure for Monoclonal Culture Stability
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Solution Overview
Problem
Conventional microtiter plates are inefficient for high-throughput cell culture experiments due to large volume requirements, evaporation issues, nutrient supply challenges, and cell migration, making it difficult to maintain consistent conditions and monoclonality for biomedical developments.
Innovation Solution
A cell cultivation apparatus with separate wells having a high aspect ratio, allowing fluid exchange, where cells are retained within the wells and connected to a common medium volume, enabling controlled fluid drainage and analysis of metabolic products.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If conventional microtiter plates are used for cell culture, then cell culture experiments can be performed, but large volumes of reagents are required per well and the plates are relatively large making cell location time-consuming
Solution Approach 1:
The device segments the cell culture system into numerous small wells (e.g., 1536 or more) arranged in a compact format, allowing individual cell isolation and study in minimal volume while maintaining high throughput capability
Solution Approach 2:
The invention transitions from traditional 2D microtiter plate formats to a 3D well structure with specific depth-to-diameter ratios, enabling cells to be retained at the bottom while allowing medium exchange through the well structure, thus reducing reagent volume requirements
2Quantity of substance
If highly miniaturized wells are used to reduce volume, then reagent consumption is reduced, but challenges arise regarding evaporation, nutrient supply, concentration of metabolic products, and cell migration
Solution Approach 1:
The invention optimizes the depth-to-diameter ratio of wells to a specific range (1:1 to 10:1) to balance multiple parameters: sufficient medium volume for nutrient supply, adequate surface area for gas exchange, and appropriate volume for metabolic product accumulation, thereby maintaining reliable cell culture conditions in miniaturized format
Solution Approach 2:
The well structure acts as an intermediary between the cells and the external environment, controlling medium exchange, preventing evaporation through proper well depth, and managing metabolic product concentration while maintaining cell retention
3Productivity
If cells are cultured in conventional microtiter plates, then cell culture can be performed, but cell migration occurs due to turbulence during refilling, movement of supports, heating, and convection, making it difficult to maintain monoclonality
Solution Approach 1:
The invention creates localized stable environments in each well with optimized geometry that minimizes fluid dynamics-induced cell migration, while the overall system maintains high throughput capability through parallel processing of numerous wells
Solution Approach 2:
The well design preemptively counteracts cell migration by creating a depth-to-diameter ratio that prevents cells from escaping during medium exchange, turbulence, or device movement, thereby maintaining monoclonality before problems can occur
4Duration of action of moving object
If separate wells with high aspect ratio are used to retain cells, then cells can be identified and observed over longer periods, but device complexity increases
Solution Approach 1:
The invention uses a specific depth-to-diameter ratio parameter range (1:1 to 10:1) that provides sufficient cell retention and observation capability while avoiding excessive structural complexity that would complicate manufacturing and operation
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
Facilitates high-throughput cell culture by maintaining cells in separate wells with minimal evaporation and nutrient loss, allowing for prolonged observation and analysis of metabolic products, while ensuring consistent conditions and monoclonality.
Implementation Method 1
The wells have a large aspect ratio (depth to diameter), which retains cells within the wells and/or suppresses the release of cells from the wells into the larger volume in contact with them
Implementation Method 2
either metabolic products can accumulate separately in each well and be assigned to the well and the cells contained therein
Implementation Method 3
or particularly constant conditions can be created through rapid exchange of medium and removal of metabolic products
Data Source
Figure 1~2
Figure 3~4D
Figure 5~7
AI summary
The invention relates to a carrier which is suitable for the cultivation of cells and is preferably a plate-shaped carrier, e.g. made of glass, silicon or plastic or a combination thereof, in which carrier at least one first recess is formed which extends over a first thickness portion of the carrier, wherein an array of second recesses extends from the first recess into a second thickness portion of the carrier adjacent to the first thickness portion. The first thickness portion may have a thickness of a few micrometres to several centimetres. The second recesses, which extend from a first recess into the second thickness portion and each form a second array, form cups which are suitable for receiving cells and/or synthetic particles, e.g. made of plastic or glass.