Mass Spectrometer Dynamic Ion Control for Detector Saturation

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Solution Overview

Problem

Mass spectrometry faces challenges in accurately identifying and quantifying proteins due to the high dynamic range of ion intensities in biological samples, which can lead to saturation of detectors for high-intensity peaks and under-representation of low-intensity peaks, especially in data-independent analysis.

Innovation Solution

The method involves controlling the amount of fragmented ions for each precursor mass segment based on intensity values from the MS1 spectrum, using techniques like adjusting injection time or number of ion pulses, and processing segments in order of intensity classes to ensure equal representation across the dynamic range, allowing for more precise MS2 scans.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional mass spectrometry analyzes all precursor ions uniformly, then the detection process is simple, but high-intensity peaks saturate detectors and low-intensity peaks are under-represented

Engineering Contradiction:
Improvedetection accuracyVSAvoiddynamic range coverage
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The mass spectrum is divided into multiple precursor ion mass ranges (segments), and each segment is analyzed separately with optimized acquisition parameters. This segmentation allows the system to handle different intensity ranges effectively, preventing detector saturation for high-intensity peaks while ensuring adequate detection of low-intensity peaks in other segments.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The acquisition parameters (such as injection time, ion packet size, or detector gain) are dynamically adjusted based on the intensity characteristics of each precursor ion mass range segment. This dynamic adaptation enables the system to optimize detection for each segment's specific intensity profile, resolving the contradiction between preventing saturation and detecting low-intensity signals.

Inventive Principle:
Principle #15Dynamics

2Adaptability or versatility

If data-independent analysis is performed across the entire mass range, then comprehensive coverage is achieved, but the dynamic range requirement becomes excessively high

Engineering Contradiction:
Improvemass range coverageVSAvoiddetector linearity
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The full mass range is segmented into multiple precursor ion mass ranges, each analyzed independently. This approach maintains comprehensive coverage while reducing the dynamic range requirement for each individual analysis, as each segment contains a narrower intensity distribution that fits within detector linear range.

Inventive Principle:
Principle #1Segmentation

3Ease of operation

If uniform ion injection is used for all precursor ions, then the process is straightforward, but low-intensity peaks are under-represented in the MS2 spectrum

Engineering Contradiction:
Improveacquisition simplicityVSAvoidlow-intensity peak detection
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The ion injection parameters are dynamically adjusted based on the intensity characteristics of each precursor ion mass range segment. For segments with lower intensity signals, the system increases injection time or ion packet size to enhance signal strength, while maintaining straightforward operation through automated parameter selection based on MS1 spectrum analysis.

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 the dynamic range of mass spectrometry, ensuring that both high and low-intensity peaks are accurately detected and represented, improving the identification and quantification of proteins in biological samples.

Implementation Method 1

mass analyzing the precursor ions across the mass range of interest, to obtain an MS1 mass spectrum of the precursor ions

Methodology Applied
Scientific EffectMass spectrometry:

Implementation Method 2

fragmenting the precursor ions within that precursor mass segment

Methodology Applied
Scientific EffectIon fragmentation:

Implementation Method 3

mass analyzing the amount of fragmented ions

Methodology Applied
Scientific EffectMass spectrometry:

Data Source

PatentUS11688594B2Mass spectrometer and method of mass spectrometry
Publication Date: 2023.06.27 THERMO FISHER SCI BREMEN
  • US11688594B2 patent drawing
  • US11688594B2 patent drawing
  • US11688594B2 patent drawing

AI summary

A method of mass spectrometry for analyzing a sample within a mass range of interest includes the steps: ionizing the sample to produce a plurality of precursor ions; performing an MS1 scan of the precursor ions comprising mass analyzing the precursor ions across the mass range of interest, to obtain an MS1 mass spectrum of the precursor ions; determining ion intensity values within the MS1 mass spectrum; selecting precursor mass segments within the mass range of interest, and for each precursor mass segment: fragmenting the precursor ions within that precursor mass segment; and performing an MS2 scan of the fragmented ions by: controlling an amount of fragmented ions for that precursor mass segment, based on an intensity value for that precursor mass segment derived from the MS1 spectrum; and mass analyzing the amount of fragmented ions.