Hydrophilic Polymer Layer Captures EpCAM-Negative Cancer Cells

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Solution Overview

Problem

Current methods for capturing cancer cells from blood, such as the CellSearch System, are limited in capturing various types of cancer cells, particularly those not expressing EpCAM, due to the small number and difficulty in separation from blood components.

Innovation Solution

A method involving centrifugation of blood at 1000 to 3000 G to separate specific cells onto a hydrophilic polymer layer, formed from polymers like poly(meth)acryloylmorpholine, which effectively captures cancer cells by reducing adhesion of blood cells and selectively retaining specific cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If antigen-antibody reaction (capture by EpCAM antibody) is used to capture cancer cells, then cancer cells expressing EpCAM can be captured, but the type of cancer cells that can be captured is limited

Engineering Contradiction:
Improvetype of cancer cells that can be capturedVSAvoidcapture mechanism complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent changes the capture mechanism from specific antigen-antibody reaction to physical centrifugal separation based on cell density and size differences. By adjusting centrifugal force parameters (1000-3000 G), the method can capture various types of cancer cells regardless of EpCAM expression status, thereby improving adaptability without increasing device complexity

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent replaces the biochemical capture mechanism (antigen-antibody reaction) with a mechanical separation system (centrifugal force). This substitution allows capture of diverse cancer cell types through physical properties rather than specific molecular markers, expanding the range of capturable cell types while simplifying the capture process

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

2Manufacturing precision

If centrifugation is performed at high centrifugal force to separate cancer cells from blood components, then separation efficiency is improved, but cancer cells may be damaged or lost

Engineering Contradiction:
Improveseparation efficiencyVSAvoidcancer cell integrity
Core Design Contradiction:
Manufacturing precisionVSReliability

Solution Approach 1:

The patent optimizes centrifugal force parameters to a specific range (1000-3000 G) that provides sufficient separation efficiency while maintaining cancer cell integrity. This parameter optimization resolves the contradiction by finding the optimal balance between separation performance and cell preservation

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent applies centrifugal force that is sufficient but not excessive for separation purposes. By using moderate centrifugal forces within the specified range rather than maximum possible forces, the method achieves adequate separation while avoiding cell damage

Inventive Principle:
Principle #16Partial or excessive action

3Reliability

If blood is centrifuged at low centrifugal force to preserve cell integrity, then cancer cell damage is reduced, but separation efficiency from blood components decreases

Engineering Contradiction:
Improvecancer cell integrityVSAvoidseparation efficiency
Core Design Contradiction:
ReliabilityVSManufacturing precision

Solution Approach 1:

The patent identifies and applies the optimal centrifugal force range (1000-3000 G) that simultaneously achieves both good separation efficiency and cell integrity preservation. This parameter optimization resolves the contradiction by demonstrating that moderate centrifugal forces can achieve both objectives

Inventive Principle:
Principle #35Parameter changes

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

This method enhances the capture of cancer cells, including those not expressing EpCAM, by improving separation and reducing adhesion of blood cells, allowing for more accurate analysis and drug efficacy testing.

Implementation Method 1

capturing specific cells therefrom onto a hydrophilic polymer layer... reducing adhesion or attachment of blood cells including red and white blood cells and platelets

Methodology Applied
Scientific EffectHydrophilic interaction: Hydrophile

Implementation Method 2

centrifuging sampled blood at a centrifugal force of 1000 to 3000 G... improved separation of specific cells from red and white blood cells

Methodology Applied
Scientific EffectCentrifugal force: Centrifugal Force

Data Source

PatentEP3527986B1Method for capturing specific cells
Publication Date: 2022.08.03 SUMITOMO RUBBER INDUSTRIES LTD
  • EP3527986B1 patent drawingFigure 1(a)~1(b)
  • EP3527986B1 patent drawing
  • EP3527986B1 patent drawing

AI summary

The present invention provides a method for capturing specific cells (e.g. many types of cancer cells, including cancer cells not expressing EpCAM) and a method for analysis of specific cells involving the method. Included is a method for capturing specific cells present in blood or biological fluid, the method including: centrifuging sampled blood or biological fluid at a centrifugal force of 1000 to 3000 G; and capturing specific cells therefrom onto a hydrophilic polymer layer.