Quadrupole RF Frequency Switching for Multi-Pass MSn Isolation

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Solution Overview

Problem

Conventional mass spectrometers face challenges in performing higher-order MSn analyses (where n≥3) due to limitations in quadrupole mass filter and analyzer performance, particularly in optimizing RF drive frequencies for varying m/z ranges, which hinders the efficient isolation and analysis of multiple generations of fragment ions.

Innovation Solution

Operating a quadrupole mass spectrometer with analog RF circuitry capable of resonating at multiple discrete frequencies allows for optimized RF drive frequency selection for each m/z range, enabling multi-pass MSn experiments by adjusting the RF frequency to optimize isolation and transmission of ions at each stage of fragmentation or reaction.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Device complexity

If a fixed RF drive frequency is used in the quadrupole mass filter, then the device complexity is reduced, but the ability to optimize isolation and transmission for varying m/z ranges deteriorates

Engineering Contradiction:
ImproveRF circuitry complexityVSAvoidOptimization for varying m/z ranges
Core Design Contradiction:
Device complexityVSAdaptability or versatility

Solution Approach 1:

The patent implements dynamic RF frequency selection by enabling the quadrupole mass filter to switch between multiple discrete RF drive frequencies based on the m/z range of ions being analyzed. This allows the system to adapt its operating parameters in real-time, optimizing isolation and transmission for different mass ranges without requiring a completely different device configuration for each range.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The patent changes the RF drive frequency parameter to match different m/z ranges. By selecting from multiple discrete frequencies, the system optimizes the quadrupole's mass filtering performance for specific mass ranges, improving both isolation precision and ion transmission efficiency without increasing physical device complexity.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If multiple discrete RF frequencies are supported, then the optimization for each m/z range is improved, but the device complexity increases

Engineering Contradiction:
ImproveIsolation precisionVSAvoidRF circuitry complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The system dynamically selects from multiple discrete RF frequencies based on the analysis requirements, allowing optimal isolation precision for each m/z range while managing complexity through controlled switching rather than simultaneous support for all frequencies.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The quadrupole mass filter is designed with multi-functionality to operate at multiple discrete RF frequencies, enabling a single device to perform optimized analysis across different m/z ranges. This universal design allows the same hardware to adapt to various analytical requirements without requiring separate specialized devices for each frequency range.

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

3Productivity

If the RF frequency is adjusted for each m/z range, then the ion transmission is improved, but the time required for frequency switching increases

Engineering Contradiction:
ImproveIon transmission efficiencyVSAvoidFrequency switching time
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The system employs periodic scanning through discrete m/z ranges, with RF frequency adjusted in a systematic sequence. This periodic approach allows for efficient time management, where frequency switching occurs in a predetermined pattern that minimizes idle time and maximizes overall ion transmission efficiency across the full mass range.

Inventive Principle:
Principle #19Periodic action

Solution Approach 2:

The system pre-establishes discrete RF frequency settings for different m/z ranges, allowing rapid switching between predefined configurations rather than continuous adjustment. This preliminary setup of discrete frequency points reduces the time required for frequency changes during analysis.

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 enables efficient and optimized multi-pass MSn experiments by ensuring optimal RF drive frequencies for each m/z range, improving the resolution and transmission of ions, thereby enhancing the ability to identify and quantify analytes through multiple stages of ion fragmentation or reaction.

Implementation Method 1

Operating a quadrupole mass spectrometer with analog RF circuitry capable of resonating at multiple discrete frequencies allows for optimized RF drive frequency selection for each m/z range

Methodology Applied
Scientific EffectResonance: Resonance

Implementation Method 2

These precursor ions are then fragmented or otherwise reacted using one or more processes, and the fragment ions or reaction-product ions are mass analyzed

Methodology Applied
Scientific EffectCollision-induced dissociation:

Data Source

PatentUS20230386819A1Methods and apparatus for msn mass spectrometry
Publication Date: 2023.11.30 THERMO FINNIGAN LLC
  • US20230386819A1 patent drawing
  • US20230386819A1 patent drawing
  • US20230386819A1 patent drawing

AI summary

A mass spectrometry method comprises: choosing an RF drive frequency that best optimizes isolation of a precursor ion species of interest by a quadrupole mass filter (QMF); isolating the precursor ion species by passing ions through the QMF while the chosen RF drive frequency is applied thereto; fragmenting the precursor ion species, thereby generating a plurality of first-generation fragment ion species; returning the plurality of first-generation fragment ion species to an inlet end of the QMF; choosing a second quadrupole RF drive frequency that best optimizes isolation of a first-generation fragment ion species of interest by the QMF; isolating the first-generation fragment ion species of interest by passing the fragment ions through the QMF while the second chosen RF drive frequency is applied thereto; fragmenting the chosen first-generation fragment ion species of interest, thereby generating a plurality of second-generation fragment ion species; and mass analyzing the second-generation fragment ion species.