Heteropolyacid Lanthanide Staining Solution for TEM

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Solution Overview

Problem

Current staining agents for transmission electron microscopy, such as uranyl acetate, pose safety and disposal challenges due to their radioactive nature, and alternative substances like samarium and gadolinium salts provide only fairly good staining efficiency without fixative properties, necessitating the development of more effective contrast media.

Innovation Solution

A solution comprising a heteropolyacid, specifically phosphotungstic acid or phosphomolybdic acid, combined with lanthanide salts in a hydroalcoholic solvent, which forms chemically stable lanthanide polyoxometalates, enhancing staining efficiency comparable to or exceeding that of uranyl acetate.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If uranyl acetate is used as a staining agent, then staining efficiency and contrast resolution are improved, but safety risks and disposal costs increase due to radioactive nature

Engineering Contradiction:
Improvestaining efficiencyVSAvoidradioactive safety risks
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent replaces expensive, hazardous uranyl acetate with cheaper, non-radioactive heteropolyacid alternatives that achieve comparable staining efficiency. The solution uses phosphotungstic acid or phosphomolybdic acid combined with lanthanide salts, providing a disposable, safe alternative that eliminates long-term radioactive disposal concerns while maintaining image quality

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent changes the chemical parameters of the staining solution by substituting uranium-based compounds with heteropolyacids and lanthanide salts. This parameter change maintains the essential staining function while eliminating radioactivity. The specific formulation uses heteropolyacids (H3PM12O40) with lanthanide salts at controlled concentrations and pH levels (4-6) to optimize staining performance without radioactive hazards

Inventive Principle:
Principle #35Parameter changes

2Object-affected harmful factors

If alternative staining agents like samarium or gadolinium salts are used, then safety risks are reduced, but staining efficiency and fixative properties deteriorate

Engineering Contradiction:
Improveradioactive safety risksVSAvoidstaining efficiency
Core Design Contradiction:
Object-affected harmful factorsVSMeasurement precision

Solution Approach 1:

The patent creates a composite staining solution by combining heteropolyacids with lanthanide salts. This composite formulation synergistically combines the safety advantages of non-radioactive materials with enhanced staining efficiency. The heteropolyacid provides the base contrast while the lanthanide salt enhances binding affinity and fixative properties, achieving superior performance compared to either component alone

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The heteropolyacid acts as an intermediary that bridges the gap between safety and performance. It provides a non-radioactive foundation that can be enhanced with lanthanide salts, mediating between the safety requirements (no uranium) and performance requirements (staining efficiency). This intermediary approach allows the use of safe materials while achieving uranyl acetate-level performance through the combined chemical system

Inventive Principle:
Principle #24Intermediary (Mediator)

3Object-affected harmful factors

If heteropolyacids are used alone as staining agents, then safety is improved, but staining efficiency remains insufficient

Engineering Contradiction:
Improveradioactive safety risksVSAvoidstaining efficiency
Core Design Contradiction:
Object-affected harmful factorsVSMeasurement precision

Solution Approach 1:

The patent merges heteropolyacids with lanthanide salts to create a synergistic staining solution. The heteropolyacid provides safety and base contrast, while the lanthanide salt contributes enhanced binding properties and fixative capabilities. This merging of two separate chemical systems achieves staining efficiency comparable to or exceeding uranyl acetate while maintaining non-radioactive safety

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The combined heteropolyacid-lanthanide salt solution achieves multi-functionality, serving as both a safe contrast agent and an effective fixative. This universal solution replaces multiple separate steps or materials (staining agent plus fixative) with a single composite formulation that performs both functions, achieving uranyl acetate-level performance without radioactive hazards

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

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 combination of heteropolyacids with lanthanide salts in a hydroalcoholic solvent achieves better staining efficiency and contrast resolution than existing commercial solutions, including uranyl acetate, while being safer and more cost-effective.

Implementation Method 1

A solution comprising a heteropolyacid, specifically phosphotungstic acid or phosphomolybdic acid, combined with lanthanide salts in a hydroalcoholic solvent, which forms chemically stable lanthanide polyoxometalates

Methodology Applied
Scientific EffectChemical reaction: Chemical Bonding

Data Source

PatentEP3658886B1Contrast solution
Publication Date: 2022.06.15 FOND INST ITAL DI TECH
  • EP3658886B1 patent drawingFigure 1
  • EP3658886B1 patent drawingFigure 2
  • EP3658886B1 patent drawingFigure 3

AI summary

The invention relates to a solution comprising: a heteropolyacid and a lanthanide salt in a hydroalcoholic solvent. The solution may optionally also comprise an organic or inorganic buffer with a pH comprised in the interval of 4-6, or a strong acid or base. The object of the present invention also relates to a use of said solution and any products of the reaction between the components thereof as a negative stain for biological samples, a kit containing the components or precursors of said solution and a method for preparing biological samples for analysis by transmission electron microscopy which uses said solution in at least one step.