Neutral Metal Complex Marker for CE-ICP-MS Mobility Measurement

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Solution Overview

Problem

Current methods for determining electroosmotic mobility in capillary electrophoresis-inductively coupled plasma mass spectrometry (CE-ICP-MS) couplings are inefficient due to the need for additional detectors, which introduce measurement disturbances and increase experimental complexity, and existing markers like brominated organic molecules or cobalt-acetylacetone complexes are imprecise or interact with analytes, affecting separation.

Innovation Solution

The use of a complex of 1,4,7-triazacyclononane-N,N',N''-triacetic acid with a metal ion such as gallium(III), indium(III), or iron(III) as an electrically neutral marker for electroosmotic mobility, allowing direct measurement by ICP-MS without additional detectors and minimizing interactions with analytes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If additional detectors (UV or conductivity) are used to measure electroosmotic mobility, then measurement capability is improved, but device complexity and measurement disturbances increase

Engineering Contradiction:
Improveelectroosmotic mobility measurementVSAvoiddetector system
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The ICP-MS detector is made multi-functional by detecting both analyte ions and the neutral marker complex in the same detection process. This eliminates the need for separate UV or conductivity detectors, reducing device complexity while maintaining measurement capability for electroosmotic mobility

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

Solution Approach 2:

The measurement function for electroosmotic mobility is merged with the existing ICP-MS detection system. By using a neutral marker complex that produces a detectable signal in ICP-MS, the same detector serves dual purposes: analyzing analytes and measuring electroosmotic mobility, thereby eliminating additional detectors

Inventive Principle:
Principle #5Merging (Combining)

2Measurement precision

If brominated organic molecules are used as electroosmotic mobility markers, then measurement capability is improved, but measurement precision deteriorates due to peak broadening

Engineering Contradiction:
Improveelectroosmotic mobility determinationVSAvoidpeak shape control
Core Design Contradiction:
Measurement precisionVSManufacturing precision

Solution Approach 1:

The invention changes the chemical parameters of the marker from brominated organic molecules to a metal complex (gadolinium-DOTA or gallium-DOTA). This parameter change results in a sharper, more defined peak in the ICP-MS detection, improving measurement precision by eliminating the peak broadening issue associated with organic markers

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If cobalt-acetylacetone complexes are used as markers, then electroosmotic mobility measurement is enabled, but analyte separation is affected due to interactions between marker and analytes

Engineering Contradiction:
Improveelectroosmotic mobility measurementVSAvoidanalyte separation
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The neutral marker complex acts as an intermediary substance that does not interact with analytes. By using a stable metal-DOTA complex with neutral charge, the marker serves its measurement function without interfering with the electrophoretic separation of charged analytes, thus maintaining separation reliability

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The marker complex is designed with specific local properties: neutral overall charge and high stability. These localized quality features ensure that the marker remains inert toward analytes during separation, preventing interactions that would compromise analyte separation while still enabling electroosmotic mobility measurement

Inventive Principle:
Principle #3Local quality

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 precise determination of electroosmotic mobility with reduced experimental complexity and minimal interference, providing accurate and stable measurements of electrophoretic mobility of analytes, thus improving speciation analysis in CE-ICP-MS couplings.

Implementation Method 1

The apparent mobility is therefore given by the following equation (1): μapp = μep + μeo where μeo represents mobility due to electroosmotic flow

Methodology Applied
Scientific EffectElectroosmotic flow: Electro-Osmotic Flow

Implementation Method 2

capillary electrophoresis separation step (denoted 'CE' for the English acronym 'Capillary Electrophoresis')

Methodology Applied
Scientific EffectCapillary electrophoresis: Capillary Electrophoresis

Implementation Method 3

inductively coupled plasma source mass spectrometer (called 'ICP-MS' spectrometer according to the English acronym for 'Inductively Coupled Plasma Mass Spectrometry')

Methodology Applied
Scientific EffectInductively coupled plasma mass spectrometry:

Data Source

PatentEP3819632B1Use of a nota-complex as electroosmotic mobility marker during use of capillary electrophoresis coupled with an optical or mass spectrometer
Publication Date: 2022.08.24 COMMISSARIAT A LENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES
  • EP3819632B1 patent drawingFigure 1~2
  • EP3819632B1 patent drawingFigure 3~5
  • EP3819632B1 patent drawingFigure 6a

AI summary

The invention relates to the use of a complex of 1,4,7-triazacyclononane-N,N',N"-triacetic acid with a metal ion of oxidation state +III selected from gallium(III), indium(III) and iron(III) as an electrically neutral marker of the electroosmotic mobility of analytes contained in an aqueous solution to be analyzed using a capillary electrophoresis (CE) device connected by direct coupling to a mass spectrometer selected from an inductively coupled plasma mass spectrometer (ICP-MS), an atomic emission mass spectrometer (ICP-OES) and an electrospray source mass spectrometer (ESI-MS).