Structural Isomer Quantification Using fs-LIMS Without Separation

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Solution Overview

Problem

Existing methods are unable to quantitatively analyze mixtures containing three or more structural isomers using mass spectrometry alone, requiring time-consuming and costly chemical separation steps.

Innovation Solution

A method utilizing femtosecond laser ionization mass spectrometry (fs-LIMS) with linear and quadratic chirped laser pulses for ionization, combined with statistical data analysis, allows for the quantitative analysis of structural isomers without prior separation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If chemical separation steps are used to analyze mixtures of structural isomers, then measurement precision is improved, but loss of time and device complexity increase

Engineering Contradiction:
Improvequantitative analysis precisionVSAvoidanalysis time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent extracts the separation function from the analysis process by using fs-LIMS to directly detect and quantify structural isomers in mixtures without requiring physical separation. The femtosecond laser ionization selectively ionizes different isomers based on their unique ionization cross-sections, allowing direct quantitative analysis through mass spectrometry while eliminating time-consuming chromatographic separation steps.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent replaces the mechanical separation system (chromatography columns, pumps, flow systems) with an optical detection system (femtosecond laser ionization source coupled with mass spectrometry). This substitution uses the unique mass-to-charge ratios and ionization characteristics of different isomers to achieve separation-free quantitative analysis, dramatically reducing analysis time and device complexity.

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

2Measurement precision

If chemical separation steps are used to analyze mixtures of structural isomers, then measurement precision is improved, but device complexity increases

Engineering Contradiction:
Improvequantitative analysis precisionVSAvoidsystem complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent merges the ionization source, mass analyzer, and detection system into an integrated fs-LIMS platform. The femtosecond laser directly ionizes the sample in the gas phase, and the ionized molecules are immediately analyzed by the mass spectrometer without requiring separate separation equipment. This consolidation eliminates the need for chromatography systems, reducing device complexity while maintaining quantitative precision.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The fs-LIMS system serves multiple functions simultaneously: it ionizes diverse molecular species, separates ions by mass-to-charge ratio, and quantifies multiple structural isomers in a single experiment. The mass spectrometer acts as a universal detector that can analyze different types of compounds without requiring method development or system reconfiguration, simplifying the overall analytical platform.

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Difficulty of detecting and measuring

If resonance enhanced ionization is used, then qualitative distinction of isomers is improved, but quantitative analysis capability deteriorates

Engineering Contradiction:
Improveisomer distinction capabilityVSAvoidquantification accuracy
Core Design Contradiction:
Difficulty of detecting and measuringVSMeasurement precision

Solution Approach 1:

The patent changes the ionization parameter from resonant (wavelength-specific) to non-resonant (broadband femtosecond laser) ionization. By using ultrashort laser pulses with broad spectral bandwidth, the system achieves non-selective ionization that produces consistent ion yields across different isomers. This allows quantitative analysis through direct comparison of ion signals while still maintaining the ability to distinguish isomers by their unique mass spectra and fragmentation patterns.

Inventive Principle:
Principle #35Parameter changes

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 the rapid and accurate determination of fractional abundances of multiple structural isomers in a mixture through enhanced ion yield ratios, reducing the need for chromatographic separation steps.

Implementation Method 1

The same concept has also been the basis for success of the electron impact ionization, which in fact dominated organic mass spectrometry for decades. This goal of nondiscriminatory ionization automatically excludes all techniques employing high resolution in the spectral domain. Such techniques like resonance enhanced ionization have proven very powerful for the identification of components in a mixture but not for the quantification of compositions of mixtures. This directs the interest towards ultrashort laser pulses, which combine a very high peak power with a broad spectrum enabling non-resonant and thus nondiscriminatory ionization.

Methodology Applied
Scientific EffectMultiphoton ionization: Photoionisation

Implementation Method 2

Another way to gain a multidimensional approach is coupling of a spectrally broad fs-laser system with a time-of-flight (ToF) mass spectrometer.

Methodology Applied
Scientific EffectTime of flight: Time of Flight

Data Source

PatentEP3876260B1Method and system for quantitative analysis of structurally isomeric compounds within mixtures of compounds
Publication Date: 2025.10.22 PHILIPPS UNIV MARBURG
  • EP3876260B1 patent drawingFigure 1~2A
  • EP3876260B1 patent drawingFigure 2B~2C
  • EP3876260B1 patent drawingFigure 3A~3B

AI summary

The computer implemented method provides the possibility of quantitatively determining the content of structural isomers within a mixture of compounds by mass spectroscopy without previously separating them.