Heavy Metal Ion-Hematein Complexes for 3D CT Tissue Staining

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Solution Overview

Problem

Conventional histological methods for studying tissues are limited by the production of two-dimensional images from destructive preparation of three-dimensional tissue samples, leading to information loss and diagnostic limitations, while existing contrast agents for computed tomography (CT) scans, such as iodine potassium iodide and phosphotungstic acid, struggle with providing sufficient contrast and homogeneous staining for soft tissue samples.

Innovation Solution

Development of novel heavy metal ion-hematein complexes, specifically using silver (Ag+), barium (Ba2+), lead (Pb2+), gadolinium (Gd3+), and bismuth (Bi3+) ions in combination with hematein, as contrast agents for CT scanning, which allow for homogeneous staining and compatibility with conventional histological methods, enabling detailed 3D structural information and region-of-interest investigation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of information

If conventional histological staining methods are used, then tissue samples can be prepared and examined, but only two-dimensional images are obtained from destructive preparation of three-dimensional samples, leading to information loss

Engineering Contradiction:
Improveinformation lossVSAvoidpreparation method
Core Design Contradiction:
Loss of informationVSEase of manufacture

Solution Approach 1:

The patent transitions from two-dimensional histological sections to three-dimensional computed tomography imaging. By using heavy metal ion-hematein complexes that penetrate and stain entire 3D tissue samples uniformly, the method enables CT scanning to capture comprehensive spatial information without destructive sectioning, thus preserving all anatomical details in three dimensions.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

Solution Approach 2:

The heavy metal ion-hematein complexes serve as intermediaries that bridge the gap between conventional histological staining and CT imaging. These complexes provide both the staining function needed for tissue differentiation and the X-ray contrast properties required for 3D imaging, allowing simultaneous achievement of both goals without compromise.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If existing contrast agents such as iodine potassium iodide and phosphotungstic acid are used for CT scans, then some contrast is provided, but sufficient contrast and homogeneous staining for soft tissue samples are not achieved

Engineering Contradiction:
Improvecontrast qualityVSAvoidstaining homogeneity
Core Design Contradiction:
Measurement precisionVSEase of manufacture

Solution Approach 1:

The patent changes the chemical parameters of contrast agents by using heavy metal ions (such as barium, gadolinium, bismuth) with higher atomic numbers than traditional iodine-based agents. This increases X-ray attenuation and thus contrast quality. Simultaneously, the hematein ligand ensures uniform distribution and binding to tissue components, achieving homogeneous staining throughout the sample.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention creates composite contrast agents by combining heavy metal ions with hematein ligands. This composite structure provides dual functionality: the heavy metal ion component enhances X-ray contrast through high atomic number effects, while the hematein component ensures uniform tissue penetration and binding, achieving both superior contrast and homogeneous staining simultaneously.

Inventive Principle:
Principle #40Composite materials

3Measurement precision

If heavy metal ion-hematein complexes are used as contrast agents, then enhanced contrast and homogeneous staining are achieved, but the complexity of the staining solution increases

Engineering Contradiction:
Improvecontrast enhancementVSAvoidstaining solution complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent merges multiple functions into a single staining solution: the heavy metal ion-hematein complex simultaneously provides tissue staining, X-ray contrast enhancement, and homogeneous penetration. This consolidation eliminates the need for separate contrast agent applications and simplifies the overall staining protocol despite the advanced chemistry involved.

Inventive Principle:
Principle #5Merging (Combining)

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 novel complexes provide enhanced contrast and homogeneity in CT scans, facilitating detailed 3D structural information and compatibility with conventional histological methods, thereby overcoming the limitations of existing contrast agents and staining methods.

Implementation Method 1

The complexes provide enhanced contrast and homogeneity in CT scans

Methodology Applied
Scientific EffectX-ray absorption: Absorption (EM radiation)

Data Source

PatentUS11561155B2Heavy metal ion-hematein-complexes useful as ex vivo contrast agent for a computed tomography scanning of a biological sample, ex vivo method for investigating a biological sample, and use of the complexes
Publication Date: 2023.01.24 TECHNISCHE UNIVERSITAT MUNCHEN
  • US11561155B2 patent drawing
  • US11561155B2 patent drawing
  • US11561155B2 patent drawing

AI summary

The present invention relates to specific complexes comprising heavy metal ions having an atomic number of 23 or higher and 83 or lower (in particular Ag1+, Ba2+, Pb2+, Gd3+ and Bi3+) and one or more hematein ligand(s). In particular, the invention relates to the use of the complexes as ex vivo contrast agents for a computed tomography scanning of a biological sample. Moreover, the invention relates to specific ex vivo methods for investigating a biological sample by means of computed tomography scanning methods, wherein the method comprises staining the biological sample with a solution comprising one or more of the complex(es); or wherein the method comprises staining the biological sample with a staining solution comprising hematein, and separately contacting the biological sample with one or more staining solution(s) comprising one or more heavy metal ions having an atomic number of 23 or higher and 83 or lower (in particular Ag1+, Ba2+, Pb2+, Gd3+ and Bi3+).