Melatonin Detection via Position 3 Indole Conjugation

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Solution Overview

Problem

Current melatonin detection methods are limited by long incubation times and low assay temperatures, making them inefficient for sensitive detection at temperatures above 20°C.

Innovation Solution

A melatonin derivative conjugate at position 3 of the indole ring with a linker of at least 2 carbon atoms, such as 3-(2-ethylamidoglutaric acid)-5-methoxyindole (GUS), is used in an immunobiological assay, allowing for detection or quantification at temperatures above 20°C and within 0.5 hours.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional melatonin conjugates (e.g., Melatonin-1-propionic acid) are used in immunological assays, then the assay can detect melatonin, but the incubation time is long (at least 16 hours) and the temperature must be kept at or below 20°C

Engineering Contradiction:
Improvemelatonin detection sensitivityVSAvoidincubation time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent changes the chemical structure parameters of the melatonin conjugate by modifying the conjugation position from position 1 (nitrogen) to position 3 of the indole ring, and by using a linker with at least 2 carbon atoms. This structural parameter change enables the assay to operate at higher temperatures (above 20°C) and significantly reduces incubation time from 16 hours to less than 16 hours while maintaining detection sensitivity of less than 10 pg/ml

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses a composite conjugate structure combining melatonin with a carrier molecule (such as BSA, dextran, or other carriers) through a specific linker at position 3 of the indole ring. This composite material approach creates an optimized immunogen that improves assay performance, enabling both high sensitivity and reduced incubation time compared to conventional melatonin-protein conjugates

Inventive Principle:
Principle #40Composite materials

2Measurement precision

If conventional melatonin conjugates are used, then the assay can be performed, but it requires long incubation times (at least 16 hours) and low temperatures (≤20°C)

Engineering Contradiction:
Improvemelatonin detection sensitivityVSAvoidassay temperature
Core Design Contradiction:
Measurement precisionVSTemperature

Solution Approach 1:

The patent changes the chemical structure parameters of the melatonin conjugate by modifying the conjugation position from position 1 (nitrogen) to position 3 of the indole ring, and by using a linker with at least 2 carbon atoms. This structural parameter change enables the assay to operate at higher temperatures (above 20°C) while maintaining detection sensitivity of less than 10 pg/ml

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If conventional melatonin conjugates are used, then the assay can detect melatonin, but the incubation time is extended to at least 16 hours

Engineering Contradiction:
Improvemelatonin detection sensitivityVSAvoidassay throughput
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent changes the chemical structure parameters of the melatonin conjugate by modifying the conjugation position from position 1 (nitrogen) to position 3 of the indole ring, and by using a linker with at least 2 carbon atoms. This structural parameter change reduces incubation time from 16 hours to less than 16 hours, thereby increasing assay throughput and productivity while maintaining detection sensitivity

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The optimized conjugate structure (position 3 conjugation with ≥2 carbon atom linker) is designed in advance to pre-establish optimal binding characteristics, allowing the assay to achieve high sensitivity results in reduced time, thus improving overall assay productivity

Inventive Principle:
Principle #10Preliminary action

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 approach enables highly sensitive detection of melatonin with a sensitivity of less than 10 pg/ml, significantly reducing incubation time and maintaining assay accuracy at elevated temperatures.

Implementation Method 1

The immunological detection of melatonin typically relies on specific antibodies reactive towards melatonin, which are incubated together with melatonin conjugates or melatonin radioactive labels to determine the amount of captured melatonin from samples

Methodology Applied
Scientific EffectImmunological recognition:

Data Source

PatentEP3126838B1High sensitive detection of melatonin
Publication Date: 2017.11.01 KONINKLIJKE PHILIPS NV
  • EP3126838B1 patent drawingFigure 1
  • EP3126838B1 patent drawingFigure 2
  • EP3126838B1 patent drawingFigure 3

AI summary

The present invention relates to the use of a derivative of melatonin in an assay, wherein said derivative is a conjugate at position 3 of melatonin's indole ring and wherein said conjugate comprises a linker of at least 2 carbon atoms, with the proviso that the conjugate does not comprise a polypeptide or protein antigen. The derivative preferably comprises 3-(2-ethylamidoglutaric acid)-5-methoxyindole (GUS) and is coupled to a carrier such as dextran. The invention further relates to a method for detecting and/or quantifying melatonin in a sample using a compound comprising said derivative of melatonin, a corresponding immunobio logical assay and a kit of parts for detecting and/or quantifying melatonin based on the melatonin derivative.