High-Resolution Intact IGF-I and IGF-II Quantitation Without Digestion

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Solution Overview

Problem

Existing methods for quantitatively analyzing insulin-like growth factors IGF-I and IGF-II are inefficient due to low digestion yield and non-specific enzyme cleavage, particularly in the 'bottom-up' approach, making accurate measurement challenging.

Innovation Solution

A high-resolution/high-accuracy mass spectrometric method that analyzes intact IGF-I and IGF-II proteins without fragmentation, using techniques like electrospray ionization and high-resolution mass spectrometers such as orbitrap or time-of-flight, with optional purification steps like SPE and HPLC, to detect specific ions corresponding to these proteins.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If bottom-up approach with enzymatic digestion is used to analyze IGF-I and IGF-II, then quantitation can be performed, but digestion yield is low and non-specific enzyme cleavage occurs

Engineering Contradiction:

Improvequantitation accuracyVSAvoiddigestion yield

Core Design Contradiction:

Measurement precisionVSProductivity

Solution Approach 1:

The patent inverts the traditional bottom-up proteomic approach by using top-down mass spectrometry to analyze intact IGF-I and IGF-II proteins without enzymatic digestion. This inversion eliminates the problems of low digestion yield and non-specific cleavage while maintaining quantitation capability through intact protein analysis.

Inventive Principle:

Principle #13The other way round (Inversion)

Solution Approach 2:

The patent extracts and analyzes the intact protein molecules directly from biological samples using mass spectrometry, eliminating the need for enzymatic digestion steps. This extraction of intact proteins avoids the harmful effects of enzyme cleavage and achieves accurate quantitation without compromising productivity.

Inventive Principle:

Principle #2Taking out (Extraction)

2Measurement precision

If intact protein analysis by high-resolution mass spectrometry is used, then measurement precision is improved, but device complexity and analytical challenges increase

Engineering Contradiction:

Improvequantitation accuracyVSAvoidmass spectrometry system complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent utilizes parameter changes in mass spectrometry operation, specifically adjusting mass resolution and accuracy parameters to optimize the detection of intact IGF-I and IGF-II proteins. By tuning these parameters, the system achieves high measurement precision while managing device complexity through targeted optimization rather than maximum capability.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent employs isotopically labeled standards as intermediaries to facilitate accurate quantitation of intact IGF-I and IGF-II. These standards act as mediators between the complex mass spectrometry system and the target proteins, enabling precise measurement without requiring maximum system complexity.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Measurement precision

If high-resolution mass spectrometry without fragmentation is used, then measurement precision improves, but analytical difficulty increases

Engineering Contradiction:

Improvequantitation accuracyVSAvoidanalytical challenge

Core Design Contradiction:

Measurement precisionVSDifficulty of detecting and measuring

Solution Approach 1:

The patent segments the analytical process into distinct components: sample preparation, intact protein ionization, mass spectrometry analysis, and quantitation using isotopically labeled standards. This segmentation reduces the overall analytical difficulty by addressing each component separately with optimized methods, while maintaining high measurement precision through the integrated approach.

Inventive Principle:

Principle #1Segmentation

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 precise quantitation of IGF-I and IGF-II with high accuracy and resolution, allowing for reliable measurement of these proteins in biological samples like plasma or serum, suitable for clinical and research applications.

Implementation Method 1

using techniques like electrospray ionization and high-resolution mass spectrometers such as orbitrap or time-of-flight

Methodology Applied

Scientific EffectElectrospray ionization:

Implementation Method 2

high-resolution/high-accuracy mass spectrometric method that analyzes intact IGF-I and IGF-II proteins without fragmentation

Methodology Applied

Scientific EffectMass spectrometry:

Data Source

PatentUS12493049B2Quantitation of insulin-like growth factor-I and insulin-like growth factor-II with high-resolution mass spectrometry

Publication Date: 2025.12.09 QUEST DIAGNOSTICS INVESTMENTS INC

AI summary

A method of determining the amount of an IGF-I and/or IGF-II protein in a sample using high resolution/high accuracy mass spectrometry includes enriching an IGF-I and/or IGF-II protein in a sample, ionizing an IGF-I and/or IGF-II protein from the sample to generate IGF-I and/or IGF-II protein ions, and determining the amount of IGF-I and/or IGF-II protein ions with high resolution/high accuracy mass spectrometry.