Biological Sample Preparation via Tissue Section Segmentation

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Solution Overview

Problem

Current methods for collecting biological molecules from specific tissue regions require repeated sectioning due to low molecule content in thinly stained sections, making accurate targeting difficult, while increasing section thickness leads to even staining and loss of morphological detail.

Innovation Solution

A method involving the capture of non-stained and stained tissue section images, allowing for the association and division of thicker tissue sections to collect abundant biological molecules from desired regions with precise morphological identification.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If the thickness of the tissue section is reduced to several to ten micrometers, then the tissue morphology can be recognized with a microscope, but the amount of biological molecules contained in a single collected segment becomes low

Engineering Contradiction:
Improvetissue morphology recognitionVSAvoidamount of biological molecules
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The invention divides the tissue section into multiple segments along division lines before collection. By segmenting the tissue, the method allows collection of sufficient biological molecules from a single segment while maintaining the ability to recognize tissue morphology through the divided structure, resolving the contradiction between molecule quantity and morphological detail.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention introduces a dimensional approach by creating division lines that extend through the tissue section thickness. This allows the tissue to be segmented in a way that preserves morphological information while increasing the volume of individual collectable segments, effectively adding a spatial dimension to the collection process.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

2Quantity of substance

If the thickness of the tissue section is increased to increase the amount of biological molecules, then more molecules can be obtained from a single segment, but cells and tissue become overlaid in the thickness direction making it impossible to accurately determine the position of a segment to be collected

Engineering Contradiction:
Improveamount of biological moleculesVSAvoidsegment position determination
Core Design Contradiction:
Quantity of substanceVSMeasurement precision

Solution Approach 1:

By dividing the thick tissue section into multiple segments along division lines, the invention creates distinct collectable units. This segmentation allows accurate position determination for each segment while maintaining sufficient thickness for molecule accumulation, resolving the contradiction between molecule quantity and position accuracy.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention creates a copy of the tissue section structure through the division lines, allowing the thick section to be virtually replicated into multiple thinner-like segments. This copying approach enables position determination similar to thin sections while maintaining the thickness benefits for molecule accumulation.

Inventive Principle:
Principle #26Copying

3Quantity of substance

If repeated sectioning is performed to collect sufficient biological molecules, then enough molecules can be obtained for analysis, but the time and complexity of the procedure increases

Engineering Contradiction:
Improveamount of biological moleculesVSAvoidtime for repeated sectioning
Core Design Contradiction:
Quantity of substanceVSLoss of time

Solution Approach 1:

The invention performs preliminary division of the tissue section into segments along division lines before the collection process. This preliminary action allows sufficient biological molecules to be available in each segment from the start, eliminating the need for repeated sectioning and reducing overall procedure time.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

By pre-segmenting the tissue section, the invention enables single-operation collection of sufficient molecules. The segmentation is performed in advance so that when collection occurs, adequate molecule quantity is already present in each segment, avoiding time-consuming repeated sectioning.

Inventive Principle:
Principle #1Segmentation

Data Source

PatentEP2629078B1Method for preparing biological sample
Publication Date: 2019.04.17 OLYMPUS CORPORATION(JP)
  • EP2629078B1 patent drawingFigure 1
  • EP2629078B1 patent drawingFigure 2A~2B
  • EP2629078B1 patent drawingFigure 3~4

AI summary

A sufficient amount of biological molecules are collected from a desired region in a tissue section with a single operation. Provided is a method of preparing a biological specimen including a sectioning step (S1) of sectioning biological tissue along a single cutting plane; a staining step (S2) of staining a first tissue section of two tissue sections that have been sectioned in the sectioning step (S1); a stained-image capturing step (S3) of acquiring a stained image of the stained tissue section; a non-stained-image capturing step (S4) of acquiring a non-stained image in which, with respect to a second tissue section that has been sectioned in the sectioning step (S1), division lines that divide the tissue section into a plurality of segments are defined; and associating steps (S5 and S6) of associating the non-stained image and the stained image with each other.