Multi-Well Plate Fluidic Connections for Cell Containment

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Solution Overview

Problem

Current compartmentalized cell culture substrates are inadequate for high-density, high-throughput drug screening applications due to issues such as cell migration, chemical integrity, optical interference, and compatibility with automated imaging systems, limiting their ability to model complex neurodegenerative diseases and prion-like mechanisms effectively.

Innovation Solution

A novel ANSI/SLAS compliant multi-well plate with fluidically connected wells, featuring microfabricated closed channels that prevent cell migration and maintain chemical integrity, and an optically transparent design for high-resolution imaging, compatible with commercial robotics and imaging systems, using thermoplastic materials like polystyrene and cyclo-olefin-copolymer for robust manufacturing.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If micromachined substrates are used to prevent cell migration, then cell containment is improved, but device complexity and manufacturing difficulty increase

Engineering Contradiction:

Improvecell containmentVSAvoidmicrochannel network complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The substrate is divided into multiple discrete wells separated by walls, with fluidic connections implemented as simple channels through the walls rather than complex microchannel networks. This segmentation approach maintains cell containment while simplifying the overall device structure.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The complex microchannel network is extracted and replaced with simple fluidic connections through wall openings. The essential function of preventing cell migration is maintained by removing cells from the fluidic connection path, while the complex microchannel structure is taken out and replaced with simpler geometry.

Inventive Principle:

Principle #2Taking out (Extraction)

2Reliability

If complex microchannel networks are used to establish fluidic connections, then cell containment is improved, but ease of operation deteriorates due to difficult liquid handling and bubble formation

Engineering Contradiction:

Improvecell containmentVSAvoidliquid handling

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The fluidic connections are designed with local quality variations - simple channel geometry in critical areas to prevent bubble formation, and adequate channel dimensions to facilitate liquid handling. The wall opening geometry is optimized locally to balance cell containment with ease of operation.

Inventive Principle:

Principle #3Local quality

3Ease of manufacture

If PDMS materials are used for substrate manufacturing, then ease of manufacture is improved, but manufacturing precision deteriorates due to flaccid and elastic material properties

Engineering Contradiction:

Improvesubstrate fabricationVSAvoidspatial tolerances

Core Design Contradiction:

Ease of manufactureVSManufacturing precision

Solution Approach 1:

The substrate structure employs asymmetric design where the bulk material provides mechanical stability and precision, while the fluidic connection regions provide the necessary flexibility. The wall thickness and channel geometry are asymmetrically optimized to balance manufacturing ease with spatial precision.

Inventive Principle:

Principle #4Asymmetry

4Reliability

If fluidic connections are positioned in walls between wells, then cell containment is improved, but measurement precision deteriorates due to inaccessible positions for automated imaging systems

Engineering Contradiction:

Improvecell containmentVSAvoidimaging accessibility

Core Design Contradiction:

ReliabilityVSMeasurement precision

Solution Approach 1:

The fluidic connections are positioned in the wall between wells at a height that places them within the focal plane of automated imaging systems. This dimensional positioning in the vertical axis enables both cell containment and imaging accessibility, resolving the contradiction by utilizing the third dimension.

Inventive Principle:

Principle #17Another dimension (Dimensionality change)

5Productivity

If high-density well arrays are implemented, then productivity is improved, but device complexity increases due to increased number of fluidic connections

Engineering Contradiction:

Improvescreening throughputVSAvoidfluidic connection network

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

Multiple fluidic connections are merged into shared wall structures between adjacent wells. The wall openings and channels are combined into integrated features that serve multiple wells simultaneously, reducing the total number of discrete fluidic connections while maintaining high-density well arrays.

Inventive Principle:

Principle #5Merging (Combining)

Data Source

PatentUS20230127798A1Multi-Well Plates for Creation of High-Density Arrays of Compartmentalized Cell Cultures for Usage in High Capacity Applications

Publication Date: 2023.04.27 CELLECTRICON

AI summary

The disclosure relates to multi-well plates having fluidic connections between neighboring wells that are useful to produce a cell culture substrate and compliant with American National Standards Institute of the Society for Laboratory Automation and Screening (ANSI/SLAS) microplate standards