Interlocking Microplates for Long-Term Organoid Culture and Assays
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Solution Overview
Problem
Existing methods for culturing cells in a 3D environment, such as hydrogels, face challenges in maintaining healthy cellular structures for extended periods and are labor and time-intensive, particularly in creating and sustaining organoids for biochemical assays.
Innovation Solution
A system of microplates including a starter, combination, and assay plates, designed for seamless interconnection and transfer of cells, with features like mating collars, alignment guides, and perfusable units for gravitational fluid exchange, enabling efficient growth and maintenance of organoids.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If cells are cultured in 3D hydrogels to maintain cellular behavior and morphology, then cellular structure fidelity is improved, but culture duration and cell health are reduced
Solution Approach 1:
The culture system is divided into modular microplates with individual wells, each containing separate hydrogel compartments. This segmentation allows cells to be cultured in 3D hydrogels for structural fidelity while enabling individual well management for extended culture durations through selective media changes and conditions optimization
Solution Approach 2:
The patent introduces dynamic media exchange systems where hydrogels can be replenished and conditions adjusted over time. This allows the culture system to maintain 3D structural fidelity while adapting conditions to support long-term cell health and culture duration
2Adaptability or versatility
If manual methods are used for cell deposition and culture maintenance, then flexibility in experimental design is improved, but labor intensity and time consumption increase
Solution Approach 1:
The microplate system is designed with universal features including standardized well configurations, interchangeable hydrogel formats, and adaptable media exchange protocols. This universality maintains experimental design flexibility while enabling high-throughput processing that improves productivity
Solution Approach 2:
The patent introduces automated media exchange systems and robotic handling interfaces as intermediaries between the researcher and the culture wells. These intermediaries preserve experimental flexibility by allowing programmable protocols while dramatically reducing manual labor and increasing throughput
3Adaptability or versatility
If cells are transferred between different culture plates, then culture conditions can be optimized, but transfer complexity and potential cell damage increase
Solution Approach 1:
The patent merges multiple culture conditions into a single integrated microplate system where different wells can have different hydrogel types, media compositions, and environmental conditions. This eliminates the need for physical plate transfers while maintaining culture condition optimization capabilities
Solution Approach 2:
The system employs nested structures where microplates contain multiple wells, each well contains hydrogel compartments, and hydrogels can be nested within well chambers. This nested design allows conditional optimization at multiple levels without requiring complex transfer operations between plates
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 the creation and monitoring of 3D cellular structures like organoids with improved longevity and efficiency, allowing for biochemical assays with reduced labor and time requirements.
Implementation Method 1
In another example, the combination plate and the assay plate each include a respective alignment pin and a respective alignment receiving aperture
Implementation Method 2
individual wells of the second array of wells of the starter plate include a respective starter plate mating collar being sized and shaped to create an interference fit with a respective combination plate mating collar of individual wells of the first array of wells
Implementation Method 3
a first array of wells interconnected with a second array of wells to form a gravity flow path from the first array of wells to the second array of wells
Implementation Method 4
agitating the mated plates to transfer the one or more cells included in the at least one well of the first array of wells into a corresponding at least one well of the second array of wells
Data Source
AI summary
Disclosed are various embodiments for growing, culturing, monitoring, and analyzing embryoid bodies, fused embryoid bodies, spheroids, organoids, or other multi-cellular bodies using a system of microplates. Different types of microplates are designed to be used during the various stages of growing and culturing of cells to form embryoid bodies, fused embryoid bodies, spheroids, organoids, or other multi-cellular bodies. The different microplates are designed to mate with one another to allow for the transfer of cells from wells in one plate to wells in the other plate. An assay plate includes an array of perfusable units that include a supply well that is in fluid communication with a culture well to allow for an exchange of fluid.


