Differential Chromogen Staining for Analyte Density Labeling

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Solution Overview

Problem

Current methods for determining analyte density in biological samples using single chromogen staining are limited, as they require image analysis and cannot easily distinguish between different densities, restricting measurements to a 0-255 gray-scale range and obscuring analyte density variations.

Innovation Solution

A method involving differential staining, where an enzyme capable of acting on multiple chromogens is used to generate distinct color chromogen-enzyme products, allowing for direct visualization and quantification of analyte density levels without image analysis, using a combination of first, second, and third colors proportional to analyte density.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If single chromogen staining is used, then the staining process is simple, but the ability to distinguish analyte density levels is limited

Engineering Contradiction:
Improvestaining process simplicityVSAvoidanalyte density differentiation
Core Design Contradiction:
Ease of manufactureVSMeasurement precision

Solution Approach 1:

The patent uses multiple chromogens that produce distinct color reactions (e.g., blue, red, green) to indicate different analyte density levels. The first chromogen produces a first color, the second chromogen produces a second color, and their combination produces a third color, enabling direct visual differentiation of density without complex image analysis

Inventive Principle:
Principle #32Color changes

Solution Approach 2:

The invention transitions from a single-dimension gray-scale measurement (0-255) to a multi-dimensional color space by using multiple chromogens with distinct colors. This adds a new dimension (color hue) to the measurement, allowing laboratory personnel to directly observe and distinguish different analyte density levels without requiring image analysis systems

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

2Device complexity

If single chromogen staining with gray-scale measurement is used, then the measurement system is simple, but the measurement range is limited to 0-255

Engineering Contradiction:
Improvemeasurement system complexityVSAvoidanalyte density measurement range
Core Design Contradiction:
Device complexityVSMeasurement precision

Solution Approach 1:

By using multiple chromogens that produce distinct colors, the measurement system expands from a limited 0-255 gray-scale range to a much broader color spectrum. The first chromogen produces a first color, the second chromogen produces a second color, and their combination produces a third color, providing a more granular and extensive measurement range for analyte density

Inventive Principle:
Principle #32Color changes

3Adaptability or versatility

If multiple chromogens are used to stain different analytes, then different analytes can be distinguished, but the stains obscure each other

Engineering Contradiction:
Improvemulti-analyte detection capabilityVSAvoidstain visibility
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The patent applies different chromogens in a sequential manner where the first chromogen stains areas of lower analyte density, and the second chromogen stains areas of higher analyte density. This creates a spatial differentiation where each chromogen acts in its optimal local environment, preventing mutual obscuration while maintaining versatility

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The first chromogen is allowed to act partially on the analyte, producing a first color in areas of lower density. Then the second chromogen acts on remaining areas or overlays to produce a second color or third color in areas of higher density. This partial action approach prevents complete obscuration while achieving multi-level detection

Inventive Principle:
Principle #16Partial or excessive action

4Measurement precision

If image analysis systems are used to determine analyte density, then density measurements can be obtained, but the process requires complex equipment and is not easily evaluated by direct observation

Engineering Contradiction:
Improveanalyte density measurement capabilityVSAvoidequipment requirement
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent converts the invisible gray-scale density variations into visible color changes that can be directly observed by laboratory personnel. The first chromogen produces a first color, the second chromogen produces a second color, and their combination produces a third color, making analyte density levels immediately apparent without requiring image analysis systems or complex equipment

Inventive Principle:
Principle #32Color changes

Solution Approach 2:

The invention replaces the mechanical/image analysis system with a chemical/optical system. Instead of using image analysis systems to detect and measure density variations, the patent uses chromogen-enzyme reactions that produce distinct colors proportional to analyte density, allowing direct visual evaluation and eliminating the need for complex imaging equipment

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

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

Enables accurate and easy estimation of analyte density levels in biological samples by direct observation, overcoming limitations of single chromogen staining and expanding measurement scales beyond 0-255, facilitating more precise analysis without the need for image analysis systems.

Implementation Method 1

binding an enzyme to an analyte contained in a sample, the enzyme capable of acting on at least two chromogens; incubating the sample with a first chromogen for a first time period to generate a first color chromogen-enzyme product

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Implementation Method 2

incubating the sample with a first chromogen for a first time period to generate a first color chromogen-enzyme product, the first color chromogen-enzyme product reflecting light observable as a first color

Methodology Applied
Scientific EffectChromogen-enzyme reaction: Chemical Bonding

Data Source

PatentUS10379015B2Method for labeling concentration density differentials of an analyte in a biological sample
Publication Date: 2019.08.13 DIAGNOSTIC BIOSYST
  • US10379015B2 patent drawing
  • US10379015B2 patent drawing
  • US10379015B2 patent drawing

AI summary

A method for labeling concentration density differentials of an analyte in a biological sample is provided. The method may including the steps of: binding an enzyme to an analyte contained in a sample, the enzyme capable of acting on at least two chromogens; incubating the sample with a first chromogen for a first time period to generate a first color chromogen-enzyme product, the first color chromogen-enzyme product reflecting light observable as a first color; and incubating the sample with a second chromogen for a second time period to generate a second color chromogen-enzyme product, the second color chromogen-enzyme product reflecting light observable as second color. A combination of the light observable as the first color and the light observable as the second color may be observable as a third color, and each color may describe a different analyte density in the biological sample.