Micro-fabricated Multi-well Chips for Automated C. elegans Imaging

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Solution Overview

Problem

Current methods for studying aging in C. elegans are limited by focusing on lifespan measurement alone, laborious visual observation, and lack of scalability for high-throughput analysis, which restricts the ability to track individual trajectories and monitor behavior and development effectively.

Innovation Solution

The development of scalable compositions featuring a substrate with a planar array of depressions and a moat around each depression, made from materials like polyurethane and polydimethylsiloxane, allowing for longitudinal imaging and cultivation of large numbers of organisms, including C. elegans, in a microwell assembly that conforms to standard microplate formats.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If visual observation of worms on agar plates is used, then lifespan measurement can be performed, but the process becomes laborious and subjective, reducing throughput

Engineering Contradiction:
ImprovethroughputVSAvoidlaborious visual observation
Core Design Contradiction:
ProductivityVSEase of operation

Solution Approach 1:

The patent replaces manual visual observation with automated imaging systems that capture images of worms in microplates at regular intervals. Image analysis software automatically tracks worm position, movement, and lifespan, eliminating the need for laborious manual observation while maintaining measurement accuracy and enabling high-throughput analysis

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The system enables self-service analysis where the imaging system and software automatically perform lifespan measurement and behavioral analysis without requiring manual intervention. The microplate format allows multiple samples to be processed simultaneously through automated imaging, increasing throughput while reducing operational complexity

Inventive Principle:
Principle #25Self-service

2Productivity

If standard agar plates are used for worm cultivation, then worms can be grown, but scalability for high-throughput analysis is limited

Engineering Contradiction:
ImprovescalabilityVSAvoidscalability for high-throughput analysis
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent divides the cultivation system into multiple independent microplates, each containing multiple wells that can be independently imaged and analyzed. This segmentation allows parallel processing of multiple samples simultaneously, enabling high-throughput analysis while maintaining simple individual well structures that are easy to manufacture and scale

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The microplate format serves multiple functions: it provides individual cultivation chambers for each sample, enables automated imaging, facilitates high-throughput analysis, and maintains compatibility with standard laboratory equipment. This multi-functionality achieves scalability without increasing device complexity

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Productivity

If microtiter plates under liquid culture conditions are used, then throughput increases, but worm behavior, physiology, and lifespan are changed

Engineering Contradiction:
ImprovethroughputVSAvoidworm behavior and lifespan accuracy
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent provides local quality control by allowing each well to be independently configured with appropriate media and conditions, enabling optimization for both high throughput and accurate worm phenotyping. The microplate format maintains controlled environments that preserve natural worm behavior while enabling automated high-throughput analysis

Inventive Principle:
Principle #3Local quality

4Quantity of substance

If flatbed scanners are used to image worms on standard agar plates, then tens of thousands of worms can be imaged, but frame rate is low (∼1/hr), preventing tracking of young adult animals

Engineering Contradiction:
Improvenumber of worms imagedVSAvoidframe rate
Core Design Contradiction:
Quantity of substanceVSSpeed

Solution Approach 1:

The patent replaces slow flatbed scanning with high-speed automated imaging systems capable of capturing images at frequent intervals. The microplate format enables rapid sequential imaging of multiple wells, achieving high frame rates that allow tracking of young adult animal behavior and development while maintaining the ability to image large numbers of organisms

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Data Source

PatentUS11795423B2Micro-fabricated multi-well chips for long term automated imaging of <i>C. elegans </i>growth and behavior
Publication Date: 2023.10.24 THE TRUSTEES OF THE UNIV OF PENNSYLVANIA
  • US11795423B2 patent drawing
  • US11795423B2 patent drawing
  • US11795423B2 patent drawing

AI summary

A composition, including a substrate having a planar array of depressions each defined by concave walls and a moat disposed around each depression of said array of depressions.