Tandem Mass Spectrometry Checks for Mobile Phase Solvent Delivery

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Solution Overview

Problem

Current methods for assessing if a proper mobile phase composition is delivered from a liquid sample delivery device to a mass spectrometer rely heavily on customer education and training, which can break down in multi-user environments, leading to increased risks of starting acquisitions under non-ideal conditions.

Innovation Solution

An apparatus and method using a tandem mass spectrometer to perform neutral loss scans on the ions of an aqueous mobile phase solution based on molecular weights of known solvents, determining if the solution is properly delivered by calculating the ratio of intensities from these scans, without the need to identify specific ion-molecule clusters.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If customer education and training are used to assess mobile phase delivery, then operational flexibility is maintained, but reliability deteriorates in multi-user environments

Engineering Contradiction:
Improvemobile phase delivery assessmentVSAvoidassessment system
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The mass spectrometer automatically performs self-diagnosis by analyzing the mobile phase composition without requiring user intervention or external assessment tools. The system uses its own analytical capabilities to monitor solvent delivery, making the assessment process self-service and eliminating reliance on user training.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The system continuously monitors mobile phase delivery and provides real-time feedback through automated alerts when deviations are detected. This feedback mechanism ensures reliable assessment by immediately notifying users of potential issues, replacing the delayed feedback inherent in manual training-based approaches.

Inventive Principle:
Principle #23Feedback

2Measurement precision

If manual assessment methods are used, then device complexity is minimized, but measurement precision deteriorates

Engineering Contradiction:
Improvemobile phase composition assessmentVSAvoidassessment system
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The mass spectrometer performs multiple functions: it analyzes samples, monitors mobile phase composition, and provides system diagnostics. By making the assessment capability universal and integrated into the existing instrument, high measurement precision is achieved without requiring separate dedicated assessment devices.

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

Solution Approach 2:

The system monitors changes in key parameters such as solvent mass-to-charge ratio and signal intensity to assess mobile phase delivery. By focusing on critical parameters rather than comprehensive analysis, measurement precision is maintained while avoiding unnecessary complexity.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If comprehensive monitoring is performed, then reliability is improved, but loss of time increases due to multiple scans

Engineering Contradiction:
Improvesystem readiness determinationVSAvoidtime before sample introduction
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The system performs comprehensive mobile phase monitoring and system readiness checks before sample introduction to ensure optimal conditions. By completing assessments preliminarily, reliability is improved without causing delays during actual sample analysis, as the monitoring occurs in the background before critical operations begin.

Inventive Principle:
Principle #10Preliminary action

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 provides a more objective and reliable assessment of mobile phase delivery, ensuring the system is ready for analysis and maintaining consistent conditions, reducing the risk of non-ideal acquisitions by objectively determining the presence of expected solvents and detecting potential issues like solvent changes or leaks.

Implementation Method 1

an ion source device receives aqueous mobile phase solution from the liquid sample delivery device and ionizes compounds of the aqueous mobile phase solution, producing an ion beam of aqueous mobile phase solution compounds

Methodology Applied
Scientific EffectIonization: Ionisation

Implementation Method 2

a tandem mass spectrometer performs a first neutral loss scan of the ion beam with a first neutral loss value set to a molecular weight of a first known solvent, producing a first intensity; performs a second neutral loss scan of the ion beam with a second neutral loss value set to a molecular weight of a second known solvent, producing a second intensity

Methodology Applied
Scientific EffectMass spectrometry:

Data Source

PatentEP4022668B1Method for mass spectrometry
Publication Date: 2023.11.29 DH TECH DEVMENT PTE
  • EP4022668B1 patent drawingFigure 1~2
  • EP4022668B1 patent drawingFigure 3~4
  • EP4022668B1 patent drawingFigure 5~6

AI summary

Before a sample is introduced into a liquid sample delivery device, an ion source device receives aqueous mobile phase solution from the liquid sample delivery device and ionizes compounds of the aqueous mobile phase solution, producing an ion beam. A tandem mass spectrometer performs a first neutral loss scan of the ion beam with a first neutral loss value set to a molecular weight of a first known solvent, producing a first intensity, and performs a second neutral loss scan of the ion beam with a second neutral loss value set to a molecular weight of a second known solvent, producing a second intensity. A ratio of the first intensity to the second intensity is calculated. It is determined if the aqueous mobile phase solution is properly being delivered by the liquid sample delivery device based on the ratio.