Mass Spectrometer Ion Mobility Temporal Separation

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Solution Overview

Problem

Conventional triple quadrupole mass spectrometers face limitations in Multiple Reaction Monitoring (MRM) mode, particularly in scanning for multiple reactions, leading to reduced sensitivity due to low sampling duty cycle and the need for sequential scanning of quadrupole mass filters, which is inefficient and less sensitive.

Innovation Solution

Incorporating an ion mobility spectrometer downstream of a collision or fragmentation device to temporally separate fragment ions based on their mobility, allowing for simultaneous detection of multiple ions without reducing duty cycle, combined with mass filters for specific ion transmission and detection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If a conventional triple quadrupole mass spectrometer is used in MRM mode to monitor multiple reactions, then the ability to quantify target compounds is improved, but the sampling duty cycle for each reaction decreases, leading to reduced sensitivity

Engineering Contradiction:
Improveability to monitor multiple reactionsVSAvoidsensitivity
Core Design Contradiction:
Adaptability or versatilityVSMeasurement precision

Solution Approach 1:

The invention segments the ion analysis process by introducing an ion mobility separator that spatially and temporally separates fragment ions based on their mobility characteristics. This segmentation allows multiple fragment ions from different reactions to be separated and detected simultaneously without interfering with each other, thereby maintaining high sensitivity while monitoring multiple reactions.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention adds a new dimension to the mass spectrometry analysis by incorporating ion mobility separation. Instead of relying solely on mass-to-charge ratio separation in the quadrupole mass filters, the system introduces ion mobility as an additional separation dimension. This allows simultaneous monitoring of multiple reactions by separating fragment ions in the mobility domain before detection.

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

2Adaptability or versatility

If quadrupole mass filters are scanned sequentially across the full mass to charge ratio range to record a full mass spectrum, then comprehensive mass analysis is achieved, but the duty cycle becomes relatively low, reducing sensitivity

Engineering Contradiction:
Improvefull mass spectrum coverageVSAvoidsensitivity
Core Design Contradiction:
Adaptability or versatilityVSMeasurement precision

Solution Approach 1:

The ion mobility separator performs preliminary separation of fragment ions based on their mobility characteristics before they reach the quadrupole mass filter. This preliminary action organizes the ion stream in advance, allowing the mass filter to focus on detecting specific ions of interest without needing to scan the entire mass range, thereby improving duty cycle and sensitivity.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The invention extracts and separates specific fragment ions from the complex ion mixture using ion mobility separation. By taking out and isolating particular fragment ions based on their mobility characteristics before mass analysis, the system can achieve both comprehensive analysis and high sensitivity without requiring full-range sequential scanning.

Inventive Principle:
Principle #2Taking out (Extraction)

3Measurement precision

If triple quadrupole mass spectrometers are configured for high specificity in SRM mode, then exceptional sensitivity is achieved for single reactions, but the system becomes less efficient when monitoring multiple reactions

Engineering Contradiction:
ImprovesensitivityVSAvoidefficiency in monitoring multiple reactions
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The ion mobility separator acts as an intermediary between the collision cell and the quadrupole mass filter. It pre-separates fragment ions based on mobility characteristics, reducing the complexity of the ion stream entering the mass filter. This intermediary function allows the system to maintain high sensitivity for specific reactions while improving overall efficiency when monitoring multiple reactions simultaneously.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention introduces dynamic separation capabilities through ion mobility, allowing the system to adaptively separate and analyze different fragment ions based on their mobility characteristics. This dynamic approach enables efficient monitoring of multiple reactions by continuously separating and directing different ion types to the detector without compromising sensitivity.

Inventive Principle:
Principle #15Dynamics

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 enhances sensitivity and efficiency by enabling the simultaneous detection of multiple fragment ions without duty cycle loss, improving the analysis of complex samples like peptides and proteins, and validating quantification analyses.

Implementation Method 1

an ion mobility spectrometer or separator arranged downstream of the first ion guide or the first collision, fragmentation or reaction device, the ion mobility spectrometer or separator being arranged to temporally separate product, daughter, adduct or fragment ions according to their ion mobility

Methodology Applied
Scientific EffectIon mobility separation: Electrophoresis

Implementation Method 2

Ions are fragmented in the collision cell by Collision Induced Decomposition ('CID') wherein ions undergo multiple collisions with gas molecules in the partially enclosed collision cell

Methodology Applied
Scientific EffectCollision induced decomposition: Impact Force

Data Source

PatentUS9012840B2Mass spectrometer
Publication Date: 2015.04.21 MICROMASS UK LTD
  • US9012840B2 patent drawing
  • US9012840B2 patent drawing
  • US9012840B2 patent drawing

AI summary

A mass spectrometer is disclosed comprising a first quadrupole rod set mass filter, a collision cell, an ion mobility spectrometer or separator, an ion guide or collision cell arranged downstream of the ion mobility spectrometer or separator, a second quadrupole rod set mass filter and an ion detector.