Porous Mold Spheroid Tissue Microarray for Precise Grid Positioning

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Solution Overview

Problem

Conventional spheroid tissue microarrays lack precise horizontal positioning and embedding of tissue spheroids, leading to inefficiencies in sectioning and analysis, particularly in high-throughput applications where high density and accuracy are required.

Innovation Solution

A spheroid tissue microarray with a porous mold featuring a regular grid pattern of concave wells for precise positioning of tissue spheroids, allowing for accurate alignment and embedding within a porous matrix, enabling high-density and precise sectioning and analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If conventional techniques are used to assemble tissue samples in paraffin blocks, then a large number of tissue samples can be assembled in an array, but the horizontal positioning accuracy of the samples is poor

Engineering Contradiction:
Improvenumber of tissue samplesVSAvoidhorizontal positioning accuracy
Core Design Contradiction:
Quantity of substanceVSManufacturing precision

Solution Approach 1:

The patent employs a porous mold made of porous material that allows liquid paraffin to penetrate and embed the tissue spheroids in precise grid positions. The porous structure enables the paraffin to flow through and secure the spheroids accurately at predetermined locations, resolving the positioning accuracy issue while maintaining high sample density

Inventive Principle:
Principle #31Porous materials

Solution Approach 2:

The patent pre-forms a mold with a regular array of wells or cavities at precise horizontal positions before introducing the tissue spheroids. This preliminary structuring of the mold ensures that when spheroids are placed and embedded, they achieve accurate horizontal positioning without requiring post-positioning adjustments

Inventive Principle:
Principle #10Preliminary action

2Device complexity

If spheroids are placed in a non-porous mold, then the structure is simpler, but the spheroids cannot be properly impregnated with wax for sectioning

Engineering Contradiction:
Improvemold structureVSAvoidwax impregnation effectiveness
Core Design Contradiction:
Device complexityVSReliability

Solution Approach 1:

The patent specifies using a mold made of porous material that allows liquid paraffin to penetrate through the mold structure and effectively impregnate the tissue spheroids. The porosity enables complete wax infiltration necessary for proper sectioning, while the mold maintains sufficient structural integrity for handling

Inventive Principle:
Principle #31Porous materials

3Stability of the object's composition

If spheroids are embedded in a dense matrix, then the embedding is more stable, but the density of spheroids per unit area is reduced

Engineering Contradiction:
Improveembedding stabilityVSAvoidspheroid density per unit area
Core Design Contradiction:
Stability of the object's compositionVSQuantity of substance

Solution Approach 1:

The patent uses a mold with a regular array of discrete wells or cavities, each containing a spheroid embedded in paraffin. This localized embedding approach allows high spheroid density across the array while maintaining stable individual embeddings. The porous mold material provides overall structural stability without requiring a dense continuous matrix that would reduce spheroid capacity

Inventive Principle:
Principle #3Local quality

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

The solution enables precise positioning of tissue spheroids with centers within 100 micrometers of their ideal locations, facilitating high-throughput histological analysis and multiplex staining, and allows for higher spheroid density per unit area, enhancing the accuracy and efficiency of tissue testing and imaging.

Implementation Method 1

the porosity is important and beneficial; one consequence is that the whole product in a subsequent step can be impregnated with a wax

Methodology Applied
Scientific EffectCapillary action: Capillary Action

Data Source

PatentEP3440189B1Spheroid tissue microarray and methods of manufacture
Publication Date: 2024.08.07 MICROMATRICES ASSOC
  • EP3440189B1 patent drawingFigure 1A~1B
  • EP3440189B1 patent drawingFigure 1C~1D
  • EP3440189B1 patent drawingFigure 2A~2C

AI summary

A spheroid tissue microarray comprises an array of tissue spheroids embedded within a porous mold. The product may be impregnated with a wax or resin and sectioned, and contains spheroids which are precisely located in a regular geometric grid. A method of manufacturing a spheroid tissue microarray comprises the steps of: forming a mold of porous material from liquid mold material in a casting mold, and allowing the liquid mold material to set; removing the porous mold from the casting mold; topping up the porous mold with further liquid mold material, and allowing recesses to form in the surface of the mold by the drawing-in of liquid mold material through shrinkage as the liquid mold material sets; placing tissue spheroids into the recesses in the surface of the porous mold; and sealing the tissue spheroids within the mold by topping off with liquid mold material and allowing the liquid mold material to set. An alternative method comprises the steps of: forming a mold of porous material from liquid mold material in a casting mold; allowing the liquid mold material to set; removing the porous mold from the casting mold; placing spheroids in recesses at the bases of wells in the mold of porous material; and sealing the spheroids within the porous mold by adding further porous material on top of the spheroids; wherein the recesses at the bases of the wells in the porous material are formed by protrusions of the casting mold carrying further, nipple-shaped, protrusions.