APCI Mass Spectrometry for Accurate VLCFA and BCFA Detection

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Solution Overview

Problem

Current methods for quantifying very long chain fatty acids (VLCFA) and branched chain fatty acids (BCFA) are inadequate for diagnosing peroxisomal disorders, as they fail to accurately detect these fatty acids in biological samples, leading to incomplete breakdown and accumulation in patients.

Innovation Solution

The use of atmospheric pressure chemical ionization (APCI) mass spectrometry to detect and quantify VLCFA and BCFA ions in biological samples, including the application of hydrolyzing agents and purification steps to generate ions with specific mass-to-charge ratios for accurate measurement.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional mass spectrometry methods are used to detect VLCFA and BCFA, then the detection process is simple, but the measurement precision and reliability are insufficient for accurate diagnosis

Engineering Contradiction:

Improvedetection accuracy of VLCFA and BCFAVSAvoidcomplexity of mass spectrometry method

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent applies preliminary action by performing hydrolysis of fatty acid esters to free fatty acids before mass spectrometry analysis. This pre-treatment step converts bound fatty acids into detectable free forms, enabling accurate measurement of VLCFA and BCFA levels that would otherwise be undetectable or inaccurate using conventional direct injection methods.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent uses atmospheric pressure chemical ionization (APCI) as an intermediary ionization technique between the liquid sample introduction and mass analysis. APCI serves as a mediator that efficiently ionizes the fatty acid molecules in atmospheric pressure conditions, providing reliable and sensitive detection with reduced matrix effects compared to direct electrospray ionization.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Measurement precision

If sample preparation steps including hydrolysis and purification are added, then the measurement precision improves, but the productivity and time consumption increase

Engineering Contradiction:

Improvequantification accuracy of fatty acidsVSAvoidthroughput of diagnostic testing

Core Design Contradiction:

Measurement precisionVSProductivity

Solution Approach 1:

The method performs hydrolysis as a preliminary action before analysis, converting esterified fatty acids to free fatty acids. This pre-treatment ensures that all fatty acid forms are converted to a detectable state, improving quantification accuracy while the streamlined protocol maintains reasonable throughput for clinical diagnostics.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent employs atmospheric pressure chemical ionization which operates at atmospheric pressure rather than vacuum, allowing direct coupling with liquid chromatography. This parameter change in ionization conditions enables efficient sample analysis with reduced preparation complexity, balancing precision requirements with diagnostic throughput.

Inventive Principle:

Principle #35Parameter changes

3Measurement precision

If APCI mass spectrometry with hydrolysis is used, then the detection sensitivity and accuracy improve, but the ease of operation decreases due to additional preparation steps

Engineering Contradiction:

Improvedetection limit and accuracy of VLCFA/BCFAVSAvoidsimplicity of sample preparation

Core Design Contradiction:

Measurement precisionVSEase of operation

Solution Approach 1:

Hydrolysis is performed as a preliminary action to release bound fatty acids from esters. This single pre-treatment step significantly improves detection sensitivity and accuracy by making all fatty acid pools accessible to the mass spectrometer, while the simplicity of the hydrolysis procedure (using common reagents like LiOH or HCl) minimizes the increase in operational complexity.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

APCI acts as an intermediary ionization source that is more tolerant of sample matrix variations than direct ESI. This intermediary step provides robust ionization with high sensitivity and accuracy, while its compatibility with atmospheric pressure operation simplifies the overall system configuration and ease of use compared to vacuum-based ionization sources.

Inventive Principle:

Principle #24Intermediary (Mediator)

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 method enables precise detection and quantification of VLCFA and BCFA, facilitating the diagnosis and monitoring of peroxisomal disorders by accurately measuring these fatty acids in plasma or serum samples, improving diagnostic accuracy and treatment monitoring.

Implementation Method 1

subjecting one or more VLCFA and/or BCFA from the sample to an atmospheric pressure chemical ionization (APCI) source to generate one or more VLCFA and/or BCFA ions detectable by mass spectrometry

Methodology Applied

Scientific EffectChemical ionization: Ionisation

Implementation Method 2

determining the amount of one or more of the VLCFA and/or BCFA ions by mass spectrometry

Methodology Applied

Scientific EffectMass spectrometry:

Data Source

PatentUS11830715B2Mass spectrometric determination of fatty acids

Publication Date: 2023.11.28 QUEST DIAGNOSTICS INVESTMENTS INC

AI summary

The invention relates to the detection of fatty acids. In a particular aspect, the invention relates to methods for detecting very long chain fatty acids and branched chain fatty acids by mass spectrometry.