Online LC Analyte Concentration for Trace Mass Spectrometry Detection

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Solution Overview

Problem

Existing liquid chromatography (LC) systems face challenges in detecting trace impurities due to low concentration and ionization efficiency, with methods like fraction collectors and large volume injections requiring manual pre-treatment and solvent mismatch issues, limiting their effectiveness in mass spectrometry.

Innovation Solution

An automated on-line system with multiple pumps and switching valves for LC, enabling solvent exchange and concentration modes to trap and concentrate analytes in a trapping column, followed by ionization with a suitable solvent for mass spectrometry detection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If a fraction collector is used to concentrate trace components, then the detection level is improved, but manual pre-treatment is required and sample loss may occur during transfer to mass spectrometer

Engineering Contradiction:
Improvedetection levelVSAvoidmanual pre-treatment
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent combines the fraction collector, concentration system, and mass spectrometer into an integrated on-line system. The fraction collector is directly coupled to the mass spectrometer through an automated interface, eliminating manual transfer steps. The concentration process occurs in-line within the system, merging multiple operations into a single automated workflow that maintains sample integrity while improving detection sensitivity.

Inventive Principle:
Principle #5Merging (Combining)

2Loss of time

If SPE (solid phase extraction) is used for concentration, then solvent volatilization time is reduced, but various cartridges and separate automation devices are required

Engineering Contradiction:
Improvesolvent volatilization timeVSAvoidvarious cartridges and separate device
Core Design Contradiction:
Loss of timeVSDevice complexity

Solution Approach 1:

The patent employs a universal trapping column that can retain multiple types of analytes including organic compounds, pesticides, and pharmaceuticals. This single multi-functional column replaces the need for multiple specialized SPE cartridges. The automated valve system provides centralized control for solvent delivery and phase transitions, eliminating the need for separate automation devices while maintaining rapid solvent removal capabilities.

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

3Extent of automation

If LVI (large volume injection) with on-column focusing is used, then concentration and mass spectrometry can be automated, but it requires the sample to be dissolved in a solvent with low elution intensity which limits applicability

Engineering Contradiction:
Improveautomated concentration and mass spectrometryVSAvoidsolvent compatibility
Core Design Contradiction:
Extent of automationVSAdaptability or versatility

Solution Approach 1:

The patent implements a dynamic solvent exchange system that automatically adjusts solvent composition based on the analysis stage. During the trapping phase, a solvent with low elution intensity is used for on-column focusing. Then, through automated valve switching, the system dynamically transitions to a solvent with high elution intensity to elute the concentrated analytes. This dynamic adaptation allows the system to maintain automation while being compatible with diverse sample types and solvents.

Inventive Principle:
Principle #15Dynamics

4Ease of operation

If the solvent used in LC is used directly for MS detection, then the process is simplified, but the solvent is not advantageous for ionization and detection efficiency is reduced

Engineering Contradiction:
Improveprocess simplificationVSAvoidionization efficiency
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent employs parameter changes in solvent composition to optimize both LC separation and MS detection. After analytes are concentrated in the trapping column, the system automatically changes the solvent parameters by introducing a second solvent that is volatile and favorable for ionization. This parameter transition occurs through automated valve switching, maintaining process simplicity while dramatically improving ionization efficiency and detection sensitivity in the mass spectrometer.

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

The system allows for efficient concentration and detection of trace components without sample loss, reducing analysis time and laboratory contamination, and improving detection efficiency by automating the process.

Implementation Method 1

a solvent having an elution intensity lower than that of the first eluting solvent is supplied to the trapping column and the concentration column to trap and concentrate the analytes

Methodology Applied
Scientific EffectAdsorption: Adsorption

Implementation Method 2

The term 'on-column focusing' refers to a phenomenon that, when a solution in which a solute is dissolved in a non-eluting solvent is injected into the column, the solute is gathered at the beginning of the column as the solute does not pass through the column and only the solvent exits the column

Methodology Applied
Scientific EffectOn-column focusing:

Data Source

PatentEP3910329B1On-line system for improving detection level of analytes by liquid chromatography and analysis method using same
Publication Date: 2025.08.20 LG CHEM LTD
  • EP3910329B1 patent drawingFigure 1(a)~1(c)
  • EP3910329B1 patent drawingFigure 2~3(c)
  • EP3910329B1 patent drawingFigure 4(a)~4(c)

AI summary

An on-line system that performs concentration and solvent exchange in order to improve a detection level of analytes by a liquid chromatography (LC) is provided. The on-line system comprises: a first pump and a second pump for supplying a solvent; a liquid chromatography (LC) including a separation column (SC) connected to the first pump; a trapping column (TC) for collecting the analytes separated from the separation column; a concentration column (CC) for concentrating the analytes collected in the trapping column (TC); a detector; and first to third switching valves that communicate fluid with at least one of the first or second pumps. An analysis method using the same is also provided.