Neutral Loss Scans for Mobile Phase Delivery Verification

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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, leading to increased risks of non-ideal conditions in multi-user environments, where the level of training and knowledge is varied.

Innovation Solution

The implementation of 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 for identifying 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 of assessment deteriorates due to varied training levels in multi-user environments

Engineering Contradiction:
Improveassessment reliabilityVSAvoidsystem complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The mass spectrometer performs self-diagnosis by automatically analyzing the mobile phase composition through neutral loss scans, eliminating the need for user education and training. The system autonomously determines solvent presence and delivers quality control messages, making the assessment process independent of user expertise level.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The system implements a feedback mechanism where the mass spectrometer continuously monitors mobile phase delivery, compares detected solvent molecular weights against expected values, and provides quality control messages to indicate proper or improper delivery. This closed-loop feedback ensures reliable assessment regardless of user training.

Inventive Principle:
Principle #23Feedback

2Measurement precision

If neutral loss scans are performed to assess mobile phase delivery, then measurement precision improves, but loss of time increases due to multiple scans at different time steps

Engineering Contradiction:
Improvedelivery assessment precisionVSAvoidassessment time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The system performs neutral loss scans at multiple time steps (first, second, third time steps) before sample introduction, which is more extensive than a single scan. This excessive action ensures comprehensive assessment of mobile phase delivery and steady state achievement, with the time investment justified by the improved measurement precision and reliability.

Inventive Principle:
Principle #16Partial or excessive action

3Reliability

If steady state determination is implemented before sample introduction, then reliability of analysis conditions improves, but productivity decreases due to additional monitoring steps

Engineering Contradiction:
Improveanalysis condition reliabilityVSAvoidsample throughput
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The system performs preliminary neutral loss scans at multiple time steps before sample introduction to determine when steady state is achieved. This preliminary action ensures that all subsequent analyses are performed under reliable, consistent mobile phase delivery conditions, preventing wasted sample analyses due to improper initial conditions.

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 the mobile phase delivery, ensuring the system is ready for analysis and maintaining consistent conditions, reducing the risk of starting acquisitions under non-ideal conditions.

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, produces 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

PatentUS12191132B2Method for mass spectrometry
Publication Date: 2025.01.07 DH TECH DEVMENT PTE
  • US12191132B2 patent drawing
  • US12191132B2 patent drawing
  • US12191132B2 patent drawing

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.