Multi-Well Organoid Formation for Uniform Drug Screening
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Solution Overview
Problem
Current methods for generating three-dimensional organoids are limited by variable spheroid sizes and inability to control cell type ratios, making high-throughput screening difficult, and existing drug screening methods fail to accurately predict patient-specific responses due to reliance on two-dimensional cultures or animal models, which are costly and unreliable in predicting human toxicity.
Innovation Solution
A method involving a robotic arm to form drops of a polymeric solution with cells on a surface with a water contact angle of at least 70 degrees, allowing controlled formation of organoids in a multi-well plate, combined with oxygen sensors for real-time monitoring and high-throughput drug screening.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If hanging-drop method is used to form organoids, then organoids can be formed, but they are difficult to transfer to multi-well plates for screening purposes
Solution Approach 1:
The invention segments the organoid formation process by using separate modules: a hanging-drop module for formation and a multi-well plate module for screening. The organoids are formed in hanging drops and then transferred to multi-well plates, allowing each function to be optimized independently.
Solution Approach 2:
The invention introduces an intermediary transfer mechanism (robotic arm or automated system) that bridges the hanging-drop formation system and the multi-well plate screening system, enabling automated transfer without manual intervention.
2Quantity of substance
If AggreWell plate with array of pyramids is used, then hundreds of three-dimensional organoids can be created in one well, but it does not support high-throughput screening
Solution Approach 1:
The invention divides the screening process into two stages: first, forming multiple organoids in a hanging-drop well; second, transferring selected organoids to individual wells in a multi-well plate. This segmentation allows high-density formation while maintaining high-throughput screening capability.
Solution Approach 2:
The invention transitions from two-dimensional screening (multiple organoids in one well) to three-dimensional screening (one organoid per well in a multi-well plate), enabling automated high-throughput screening while maintaining the ability to generate multiple organoids initially.
3Ease of manufacture
If ULA surfaces are used to generate spheroids, then spheroids can be formed, but they have variable size and uncontrolled cell type ratios
Solution Approach 1:
The invention performs preliminary sorting of cells before they are deposited into hanging drops. By pre-sorting cell types and controlling the number of cells deposited, the system ensures uniform organoid size and controlled cell type ratios before the actual organoid formation begins.
Solution Approach 2:
The invention applies different properties to different parts of the system: the hanging-drop surface provides controlled cell deposition with specific cell type ratios, while the three-dimensional environment inside the drop allows natural organoid formation. This local differentiation of functions enables both control and natural development.
4Productivity
If conventional two-dimensional cell culture is used for drug screening, then screening can be performed, but it cannot accurately predict human response to drugs
Solution Approach 1:
The invention transitions from two-dimensional cell culture to three-dimensional organoid models for drug screening. The three-dimensional structure better mimics human tissue architecture and physiology, thereby improving the accuracy of predicting human response to drugs while maintaining high-throughput screening capability.
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
Enables the generation of uniform organoids for precise drug screening, distinguishing between true positive and false responses, and predicting human toxicity with high sensitivity and accuracy, reducing the need for animal testing.
Implementation Method 1
operating a robotic arm to establish a contact between a surface of the drop and a surface which is characterized by a water contact angle of at least 70 degrees
Implementation Method 2
forming at an end of a liquid channel a drop of a polymeric solution comprising cells
Implementation Method 3
embedding oxygen sensors for real-time monitoring, enabling precise drug screening and toxicity assessment
Data Source
AI summary
Methods of generating organoids on multi-well plates are provided by depositing a polymeric solution comprising cells under conditions which result in a homogenous population of organoids, which can be used for high throughput analysis for drug screening and for determining treatment regimens of a drug.