Mass Spectrometer MRM Transition Optimization

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Solution Overview

Problem

Conventional mass spectrometers require excessive time for product ion scan measurements due to numerous steps in changing mass-to-charge ratios and varying collision energies, leading to insufficient peak data points and poor reproducibility in mass chromatograms.

Innovation Solution

A mass spectrometer with a front mass separation section, fragmentation section, and rear mass separation section that performs MS n< analysis using multiple reaction monitoring (MRM) transitions, reducing the number of steps by using optimal collision energies and varying precursor ion mass-to-charge ratios, thereby shortening measurement cycles and improving data point density.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If product ion scan measurements are performed by changing mass-to-charge ratios in numerous steps and varying collision energies, then comprehensive product ion spectra can be acquired, but measurement time becomes excessively long resulting in insufficient peak data points

Engineering Contradiction:
Improveproduct ion spectrum acquisition completenessVSAvoidmeasurement cycle time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent extracts only the necessary MRM transitions from the full product ion scan by pre-selecting specific precursor ion-to-product ion transitions that are most relevant for the analysis. This eliminates the need to scan through all possible mass-to-charge ratios in numerous steps, while still capturing the essential spectral information needed for accurate compound identification and quantification.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent performs preliminary selection of optimal MRM transitions and collision energies before the actual measurement. By pre-defining the specific transitions to monitor and the collision energies to use, the system avoids time-consuming real-time optimization during the measurement cycle, thus reducing measurement time while maintaining spectral quality.

Inventive Principle:
Principle #10Preliminary action

2Reliability

If conventional product ion scan measurements are performed with multiple collision energies, then complete product ion spectra are obtained, but the number of measurement steps increases leading to poor reproducibility

Engineering Contradiction:
Improveproduct ion spectrum completenessVSAvoidmass chromatogram reproducibility
Core Design Contradiction:
ReliabilityVSManufacturing precision

Solution Approach 1:

The patent changes the approach from scanning multiple collision energies to monitoring specific MRM transitions at optimized, fixed collision energies. This parameter optimization allows the system to achieve reliable and reproducible results by focusing measurement resources on the most informative transitions rather than uniformly scanning all possible energy values.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The selected MRM transitions serve multiple functions simultaneously: they provide quantitative information, enable compound identification, and reduce measurement time. By choosing transitions that are characteristic of target compounds, the system achieves reliable spectra acquisition with fewer measurement steps, improving both completeness and reproducibility.

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

3Reliability

If MRM measurement is performed with multiple transitions for target compound identification, then false-positive results can be prevented, but measurement time increases reducing data point density

Engineering Contradiction:
Improvetarget compound identification accuracyVSAvoidmeasurement cycle duration
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent applies partial action by selecting only the essential MRM transitions needed for reliable target compound identification rather than performing exhaustive measurements of all possible transitions. By monitoring a focused set of characteristic transitions with optimized collision energies, the system prevents false-positive results while maintaining sufficient data point density for accurate quantification.

Inventive Principle:
Principle #16Partial or excessive 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 configuration allows for the acquisition of product ion spectra at a shorter interval, enhancing measurement accuracy and reproducibility by reducing the time required for data acquisition and improving the reliability of target compound screening.

Implementation Method 1

a front mass separation section in which an ion having a predetermined mass-to-charge ratio is selected as a precursor ion among ions originating from a compound contained in a sample

Methodology Applied
Scientific EffectMass separation:

Implementation Method 2

a fragmentation section in which the precursor ion selected in the front mass separation section is fragmented into product ions

Methodology Applied
Scientific EffectCollision-induced dissociation:

Implementation Method 3

a rear mass separation section in which the product ions generated in the fragmentation section are subjected to mass separation

Methodology Applied
Scientific EffectMass separation:

Data Source

PatentEP3605077B1Mass spectrometer and chromatographic mass spectrometer
Publication Date: 2023.04.26 SHIMADZU CORP
  • EP3605077B1 patent drawingFigure 1A~1C
  • EP3605077B1 patent drawingFigure 2
  • EP3605077B1 patent drawingFigure 3~4

AI summary

A mass spectrometer capable of performing an MSn analysis includes: a storage section 41 for storing an MRM measurement condition including a plurality of MRM transitions, and data for a standard multi-MRM spectrum indicating an intensity of product ions as a mass peak, the intensity of the product ions being measured under the MRM measurement conditions; a target compound input receiving section 42 for receiving an input of one or more target compounds; a measurement execution section 44 for reading the MRM measurement conditions respectively corresponding to the one or more target compounds from the storage section 41, and measuring the sample under the MRM measurement conditions; a measured multi-MRM spectrum creation section 45 for creating a measured multi-MRM spectrum indicating an intensity of product ions as a mass peak on a graph having mass-to-charge ratios of the product ions on one axis, the intensity of the product ions acquired by measuring the sample; and a similarity degree calculation section 47 for obtaining for each of the target compounds, a degree of similarity between the standard multi-MRM spectrum stored in the storage section and the measured multi-MRM spectrum.