2D LC Heart-Cut System for Matrix Interference Reduction

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Solution Overview

Problem

Current two-dimensional liquid chromatography systems face limitations in selectively analyzing materials of interest due to matrix effects, where the matrix interferes with sensitivity in mass spectrometry measurements, especially when the matrix and target material have the same elution time.

Innovation Solution

A two-dimensional liquid chromatography system is designed with a first and second switching valve configuration that allows selective re-separation of the material of interest and matrix in a second column using a diluting mobile phase, ensuring accurate elution time information and minimizing interference from eluents like water or organic solvents, thereby enhancing separation accuracy and stability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If a two-dimensional liquid chromatography system is used to remove matrix effects, then the sensitivity of mass spectrometer is improved, but the device complexity increases due to multiple columns and switching valves

Engineering Contradiction:
Improvesensitivity of mass spectrometerVSAvoiddevice complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The system divides the chromatography process into two independent dimensions: first dimension separation using a first column and second dimension separation using a second column. The switching valve system segments the flow paths to direct different portions of the first dimension eluate to different destinations (second column or waste), enabling matrix removal while maintaining manageable system complexity through modular design

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent implements two-dimensional liquid chromatography by adding a second separation dimension perpendicular to the first. Materials co-eluting in the first dimension are separated in the second dimension, effectively removing matrix effects that would otherwise interfere with mass spectrometer sensitivity

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

2Manufacturing precision

If a heart-cut method is applied to selectively re-separate material of interest, then the manufacturing precision of separation is improved, but the loss of time increases due to additional separation steps

Engineering Contradiction:
Improveseparation accuracyVSAvoidanalysis time
Core Design Contradiction:
Manufacturing precisionVSLoss of time

Solution Approach 1:

The system performs preliminary separation in the first dimension to rough-separate materials by their primary retention characteristics. This preliminary action identifies candidate materials for further analysis, allowing the heart-cut method to focus subsequent second dimension separation only on relevant time windows, thus improving separation accuracy while minimizing time loss

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

Instead of separating all materials in the first dimension eluate, the system applies partial action by using the switching valve to select only specific portions (heart-cut) containing the material of interest for further second dimension separation. This reduces the overall analysis time while maintaining high separation accuracy for the target analyte

Inventive Principle:
Principle #16Partial or excessive action

3Ease of operation

If independent one-dimensional separation is performed, then the ease of operation is improved, but the object-affected harmful factors increase due to matrix effects

Engineering Contradiction:
Improveease of operationVSAvoidmatrix effect
Core Design Contradiction:
Ease of operationVSObject-affected harmful factors

Solution Approach 1:

The switching valve acts as an intermediary device between the first column and the second column/mass spectrometer. It mediates the flow of eluate by selectively directing different time segments to different destinations, enabling the system to maintain the simplicity of independent one-dimensional separation operations while eliminating matrix effects through intelligent flow path control

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent merges two one-dimensional separation systems into a unified two-dimensional configuration. By combining the first column separation with the second column separation and using the switching valve to integrate their operations, the system achieves both the operational simplicity of independent separations and the matrix removal capability of two-dimensional chromatography

Inventive Principle:
Principle #5Merging (Combining)

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 configuration improves the accuracy and efficiency of material analysis by allowing precise separation and collection of the material of interest, reducing matrix interference and ensuring stable collection, while confirming sample integrity through mass spectrometry.

Implementation Method 1

a first column 200 primarily separating materials in an injected sample

Methodology Applied
Scientific EffectChromatography: Chromatography

Implementation Method 2

the material of interest and the matrix are separated from each other by the eluent supplied from the second mobile-phase pump again

Methodology Applied
Scientific EffectChromatography: Chromatography

Data Source

PatentUS10018603B2Two-dimensional liquid chromatography system for heart-cut method
Publication Date: 2018.07.10 KOREA RES INST OF STANDARDS & SCI
  • US10018603B2 patent drawing
  • US10018603B2 patent drawing
  • US10018603B2 patent drawing

AI summary

Provided is a two-dimensional liquid chromatography system, and more particularly, a two-dimensional liquid chromatography system capable of performing both independent one-dimensional separation through a reversed-phase or normal-phase chromatography method and two-dimensional separation for removing a matrix effect in a single system.