Horizontal Antigen Retrieval Using High-Boiling Solvents

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Solution Overview

Problem

Current antigen retrieval methods for immunohistochemical staining are energy-intensive, difficult to automate, and prone to evaporation issues, with enzymatic methods being dependent on enzyme stability and fixation time, and traditional heat-induced antigen retrieval requiring long procedures and high energy consumption.

Innovation Solution

A horizontal target retrieval method using a buffered solution with a solvent having a boiling point higher than water, which reduces the amount of solution and energy needed, eliminates the need for covering the sample, and simplifies the apparatus by heating the solution and sample above 100°C without evaporation issues.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional heat-induced antigen retrieval is used, then antigenicity is restored, but energy consumption increases and procedure time increases

Engineering Contradiction:
Improveantigenicity restorationVSAvoidenergy consumption
Core Design Contradiction:
ReliabilityVSUse of energy by moving object

Solution Approach 1:

The patent changes the boiling point parameter of the retrieval solution by using organic solvents (ethanol, isopropanol, acetone) instead of water. This allows heating to temperatures above 100°C without water evaporation, achieving effective antigen retrieval in shorter times with lower energy consumption while maintaining reliability.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent accelerates the antigen retrieval process by using organic solvents with lower boiling points than water, allowing rapid heating and treatment cycles. This rushes through the traditional lengthy heating process while maintaining effective antigenicity restoration.

Inventive Principle:
Principle #21Skipping (Rushing through)

2Reliability

If traditional heat-induced antigen retrieval is used, then antigenicity is restored, but procedure time increases

Engineering Contradiction:
Improveantigenicity restorationVSAvoidprocedure time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent changes the thermal parameters by using organic solvents that can be heated to higher temperatures without evaporation. This enables faster treatment cycles and reduces the overall procedure time while maintaining reliable antigenicity restoration.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent skips the lengthy cooling and evaporation control steps required in traditional water-based methods by using organic solvents with higher boiling points, thereby rushing through the procedure while maintaining effectiveness.

Inventive Principle:
Principle #21Skipping (Rushing through)

3Reliability

If aqueous buffer is used for heating, then antigen retrieval is effective, but evaporation occurs requiring covering

Engineering Contradiction:
Improveantigen retrieval effectivenessVSAvoidsolution evaporation
Core Design Contradiction:
ReliabilityVSLoss of substance

Solution Approach 1:

The patent changes the solvent parameter from water to organic solvents with higher boiling points. This eliminates evaporation losses during heating while maintaining antigen retrieval effectiveness, removing the need for covering.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent converts the potential harm of evaporation into a benefit by using organic solvents that naturally resist evaporation at working temperatures. This eliminates the need for covering while maintaining solution volume and effectiveness.

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

4Ease of operation

If proteolytic enzymes are used for antigen retrieval, then epitope access is improved, but enzyme stability varies with storage time

Engineering Contradiction:
Improveepitope accessVSAvoidenzyme stability
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent substitutes the biochemical mechanism of enzyme-based retrieval with a physical/chemical mechanism using organic solvents and heat. This replaces the unreliable enzyme system with a more stable physical process that does not degrade over time.

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

Solution Approach 2:

The patent changes the retrieval mechanism from enzymatic to thermal/chemical using organic solvents. This parameter change eliminates the stability issues associated with enzyme storage while maintaining effective epitope access.

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 reduces energy and reagent consumption, shortens procedure time, and simplifies the apparatus, making it more economical and efficient while minimizing human error and evaporation problems, allowing for automated and reliable antigen retrieval.

Implementation Method 1

heating the tissue or cell sample and the buffered target retrieval solution to a temperature above 100° C.

Methodology Applied
Scientific EffectHeating: Heating

Implementation Method 2

The high temperature accelerates hydrolysis of the aldehyde-induced modifications and the aldehyde released is diluted in the water

Methodology Applied
Scientific EffectHydrolysis: Hydrolysis

Data Source

PatentUS8465944B2Horizontal antigen retrieval
Publication Date: 2013.06.18 AGILENT TECHNOLOGIES INC

AI summary

The present invention relates to a method for enhancing immunoreactivity of a tissue or cell sample fixed in a fixing medium, a target retrieval composition and its use. The method comprises providing a carrier in a horizontal position, said carrier having thereon a tissue or cell sample, said tissue or cell sample being on top of the carrier; contacting substantially the tissue or cell sample side of the carrier with a buffered target retrieval solution, wherein the target retrieval solution remains otherwise exposed to the environment; heating the tissue or cell sample and the target retrieval solution to a temperature above 100° C. The invention furthermore concerns the automated immunohistochemical staining of said samples, in particular the reactivation of antigens masked by fixation.