Nanoparticle-Enhanced Histochemical Staining for Spot Reduction

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Solution Overview

Problem

Automated histochemical processes, particularly those involving elevated temperatures, often result in anomalous staining results characterized by well-defined, circular areas of reduced staining intensity, known as 'spots', which compromise the accuracy of tissue examination.

Innovation Solution

Incorporating nanoparticles, such as metal oxides like alumina, silica, and titania, into histochemical process compositions to reduce the occurrence of these spots by enhancing the thermal properties and stability of the staining solutions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If elevated temperatures are used in histochemical processing steps, then reaction kinetics and staining efficiency are improved, but anomalous staining spots appear on tissue sections

Engineering Contradiction:
Improvestaining efficiencyVSAvoidstaining uniformity
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The patent introduces surfactant-containing compositions as intermediary substances between the heating process and the tissue section. The surfactant acts as a mediator that modifies the thermal environment at the tissue-liquid interface, preventing direct harmful thermal effects while preserving beneficial reaction kinetics. This resolves the contradiction by adding a mediating substance that allows high temperature processing without spot formation.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the chemical parameters of the processing composition by adding surfactants, which alter the physical-chemical properties of the solution-tissue interface. This parameter change modifies heat transfer characteristics and surface tension, enabling uniform heat distribution that prevents spot formation while maintaining elevated temperature benefits for reaction kinetics.

Inventive Principle:
Principle #35Parameter changes

2Extent of automation

If automated staining systems are used, then labor and error rate are reduced, but anomalous spots appear under certain temperature conditions

Engineering Contradiction:
Improveautomation levelVSAvoidstaining consistency
Core Design Contradiction:
Extent of automationVSReliability

Solution Approach 1:

The surfactant composition serves as a chemical intermediary that compensates for the lack of fine-control capability in automated systems. By modifying the thermal and interfacial properties of the processing environment, the surfactant ensures reliable, spot-free staining even when automated systems operate at fixed temperature settings without manual adjustment.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Measurement precision

If high temperature processing is applied, then antigen retrieval and probe hybridization are enhanced, but circular spots with reduced staining intensity occur

Engineering Contradiction:
Improvedetection sensitivityVSAvoidstaining uniformity
Core Design Contradiction:
Measurement precisionVSManufacturing precision

Solution Approach 1:

The patent changes the physical-chemical parameters of the processing solution by incorporating surfactants, which modify heat transfer and surface properties. This parameter change enables uniform thermal distribution across the tissue section, preventing the formation of hot spots that cause circular staining defects while preserving the high temperature conditions needed for sensitive detection of antigens and nucleic acids.

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

The use of nanoparticles significantly decreases the average number of spots per slide, improving the consistency and accuracy of histochemical staining processes, especially at temperatures above ambient.

Implementation Method 1

Incorporating nanoparticles, such as metal oxides like alumina, silica, and titania, into histochemical process compositions to reduce the occurrence of these spots by enhancing the thermal properties and stability of the staining solutions

Methodology Applied
Scientific EffectThermal conduction: Conduction (thermal)

Data Source

PatentEP2995925B1Composition for histochemical processing
Publication Date: 2021.12.15 VENTANA MEDICAL SYSTEMS INC
  • EP2995925B1 patent drawingFigure 1
  • EP2995925B1 patent drawingFigure 2
  • EP2995925B1 patent drawingFigure 3

AI summary

Disclosed embodiments concern histochemical process compositions comprising at least one nanoparticle in an amount effective to reduce or substantially eliminate the average number of spots per slide that result from a sample staining protocol. The nanoparticle can be any of various nanoparticles, or combinations thereof, including metals, metal alloys, metal oxides, ceramics, functionalized metals or metalloids, and other miscellaneous nanoparticles, such as carbon nanoparticles and diamond nanoparticles. Typically, the nanoparticle concentration is from greater than zero to at least about 25 parts per million, more typically from about 2 parts per million to about 20 parts per million. Embodiments of a method for using process nanosolutions also are disclosed. One embodiment concerns applying a histochemical process composition to a sample, followed by performing a staining protocol on the sample. Particular embodiments concern automated histochemical processes comprising dispensing a nanosolution onto a sample using an automated system, heating the sample, and performing a sample staining process on the sample.