Blood Cell Aggregating Agent for CTC Paraffin Block Preparation

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Solution Overview

Problem

Conventional methods for preparing paraffin blocks from blood cells face challenges such as cell damage, loss, and low reproducibility, especially when attempting to diagnose circulating tumor cells (CTCs), due to the lack of extracellular matrix components and the complexity of existing cell aggregation methods.

Innovation Solution

A blood cell aggregating agent containing gelatin and optional additives like pectin, chondroitin sulfate, fibronectin, or laminin is used to aggregate blood cells, preventing damage and loss, and facilitating the preparation of paraffin blocks with improved sensitivity and specificity for CTC detection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If conventional methods (centrifugation, chemical treatment, micro filtration) are used to extract CTCs from blood, then CTCs can be separated from red blood cells, but white blood cells are damaged and lost during the process

Engineering Contradiction:
ImproveCTC recovery rateVSAvoidwhite blood cell loss
Core Design Contradiction:
Quantity of substanceVSLoss of substance

Solution Approach 1:

The patent introduces an extracellular matrix component (such as collagen, fibronectin, laminin, or gelatin) as an intermediary substance to replace conventional chemical treatments and micro filtration methods. This intermediary provides a gentle aggregation mechanism that preserves white blood cell integrity while enabling effective CTC separation and recovery

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the physical-chemical parameters of the blood sample by introducing extracellular matrix components that alter cell aggregation behavior. This parameter change enables separation based on cell surface properties rather than mechanical force or chemical lysis, thereby preserving cell viability and reducing loss

Inventive Principle:
Principle #35Parameter changes

2Manufacturing precision

If multiple centrifugation steps are performed to purify blood cells, then red blood cells are removed effectively, but the process becomes complex and time-consuming

Engineering Contradiction:
Improveblood cell purification qualityVSAvoidprocess complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent merges the functions of red blood cell removal and white blood cell aggregation into a single step by introducing extracellular matrix components. This combination eliminates the need for multiple sequential centrifugation steps while maintaining purification quality, thereby simplifying the overall process

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The extracellular matrix component serves multiple functions simultaneously: it aggregates white blood cells, enables CTC separation, and provides structural support for paraffin block formation. This multi-functionality replaces several separate processing steps with a single versatile reagent

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

3Quantity of substance

If blood cells are aggregated using conventional methods, then cells can be concentrated for analysis, but cell damage and loss occur

Engineering Contradiction:
Improvecell concentrationVSAvoidcell integrity
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The extracellular matrix component acts as a gentle intermediary that mediates cell aggregation through natural adhesion mechanisms rather than harsh mechanical or chemical forces. This preserves cell integrity while achieving effective concentration for downstream analysis

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent converts the naturally occurring tendency of blood cells to aggregate (which can lead to clogging and loss) into a beneficial feature by using extracellular matrix components to guide controlled aggregation. This transforms a potential harm into a useful concentration mechanism that preserves cell viability

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

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 method enhances the reproducibility, sensitivity, and specificity of CTC detection by maintaining cell integrity and reducing the need for multiple centrifugation steps, allowing for the effective preparation and analysis of paraffin blocks from small blood samples, enabling accurate histological, immunohistochemical, and molecular biological analyses.

Implementation Method 1

a blood cell aggregating agent for preparing a paraffin block, comprising a material for aggregating blood cells

Methodology Applied
Scientific EffectAdhesion: Adhesive

Implementation Method 2

the material for aggregating blood cells performs functions of an extracellular matrix to aggregate the blood cells and prevent damage and loss of the blood cells

Methodology Applied
Scientific EffectPhysical protection through matrix embedding: Physical Containment

Data Source

PatentUS10656058B2Blood cell aggregating agent for preparing paraffin block and method for preparing paraffin block by using same
Publication Date: 2020.05.19 NATIONAL CANCER CENTER(JP)
  • US10656058B2 patent drawing
  • US10656058B2 patent drawing
  • US10656058B2 patent drawing

AI summary

The present invention relates to a material for aggregating blood cells, used in the preparation of a paraffin block for diagnosing circulating tumor cells (CTCs), and a method for preparing a paraffin block using the same, and more specifically, to a method for detecting CTCs present in the blood through blood sample collection in the preparation of a paraffin block from CTCs, which are present in a very small amount in the blood. The present invention is non-invasive and simple, and thus is very useful for the diagnosis of cancer recurrence and metastatic cancer and for prognosis prediction, and can be a remarkable breakthrough in cancer treatment through the analysis of the onset, metastasis and recurrence mechanisms of cancer.