Tandem Mass Spectrometry Ion Ejection Control

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Solution Overview

Problem

Current tandem mass spectrometry methods face limitations in efficiently analyzing samples due to the need for large quantities of precursor ions and challenges in dynamically ranging parallel ion accumulation and sequential ejection, which restricts the instrument's duty cycle and analytical capabilities.

Innovation Solution

The method involves injecting ions into a device capable of serial ejection using a pseudopotential barrier generated by an RF voltage, filtering ions upstream to manage m/z-dependent accumulation, and sequentially ejecting ions based on their mass-to-charge ratios for individual analysis, allowing for improved dynamic range and predictable ejection without relying on ion mobility measurements.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If parallel ion accumulation is used to increase sensitivity, then the quantity of precursor ions is improved, but the dynamic range control becomes difficult and the ejection timing becomes unpredictable

Engineering Contradiction:
Improvequantity of precursor ionsVSAvoiddynamic range control
Core Design Contradiction:
Quantity of substanceVSMeasurement precision

Solution Approach 1:

The patent segments the continuous ion beam into discrete m/z-dependent groups using a quadrupole mass filter with notched isolation waveforms. This segmentation allows precise control over which ion species are accumulated and when they are ejected, resolving the dynamic range control issue while maintaining high ion quantities through parallel accumulation of multiple m/z windows.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent applies preliminary filtering and sorting of ions by m/z ratio before accumulation using the quadrupole mass filter. By pre-organizing ions into discrete m/z groups with notched isolation waveforms, the system ensures predictable ejection timing and accurate dynamic range control while still accumulating large quantities of ions in parallel.

Inventive Principle:
Principle #10Preliminary action

2Measurement precision

If sequential ejection of ions is implemented to improve dynamic range, then the measurement precision is improved, but the spectral acquisition time increases

Engineering Contradiction:
Improvedynamic rangeVSAvoidspectral acquisition time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent implements periodic ejection of ion groups based on their m/z ratios using synchronized notched isolation waveforms. Multiple m/z windows are accumulated in parallel and then ejected in a periodic sequence, maintaining predictable timing relationships that minimize spectral acquisition time while preserving accurate dynamic range control.

Inventive Principle:
Principle #19Periodic action

Solution Approach 2:

The patent maintains continuous ion accumulation across multiple parallel m/z windows rather than sequentially processing single ions. The quadrupole mass filter continuously filters and accumulates ions from multiple m/z ranges simultaneously, and the synchronized ejection mechanism ensures continuous useful action with minimal idle time between acquisitions.

Inventive Principle:
Principle #20Continuity of useful action

3Adaptability or versatility

If ion mobility measurements are used for ejection control, then the separation capability is improved, but the device complexity and requirement for additional measurements increases

Engineering Contradiction:
Improveseparation capabilityVSAvoiddevice complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent extracts the m/z ratio information directly from the quadrupole mass filter's native filtering capability and uses it for ejection control. By taking out and utilizing the already-measured m/z ratios through notched isolation waveforms, the system achieves precise separation and ejection control without adding ion mobility measurement devices or complexity.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The quadrupole mass filter performs self-service by using its own m/z filtering capability to both select ions for accumulation and control their ejection timing. The notched isolation waveforms leverage the filter's inherent mass selection property, eliminating the need for separate ion mobility measurement systems and reducing overall device complexity.

Inventive Principle:
Principle #25Self-service

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 mass spectrometer's duty cycle by reducing average spectral acquisition times and improving sensitivity, enabling more efficient analysis of complex samples with better dynamic range and applicability to uncharacterized molecules.

Implementation Method 1

injecting ions into a device capable of serial ejection using a pseudopotential barrier generated by an RF voltage

Methodology Applied
Scientific EffectPseudopotential barrier: Potential Well

Implementation Method 2

filtering ions upstream to manage m/z-dependent accumulation

Methodology Applied
Scientific EffectMass filtering: Electromagnetic Induction

Data Source

PatentUS10665441B2Methods and apparatus for improved tandem mass spectrometry duty cycle
Publication Date: 2020.05.26 THERMO FINNIGAN LLC
  • US10665441B2 patent drawing
  • US10665441B2 patent drawing
  • US10665441B2 patent drawing

AI summary

A method for parallel accumulation and serial fragmentation of ions, wherein ions are injected into a device capable of serial ejection using a pseudopotential barrier created by an RF voltage. In all instances, the ions may be filtered prior to accumulation in the device capable of serial ejection. In some cases this filtering may take the form of discrete isolation windows using isolation waveforms with multiple notches. In some cases these waveforms may be applied to a quadrupole mass filter. Following accumulation of the precursor ions, the initial population may be serially ejected using a pseudopotential barrier created by an RF voltage. Following serial ejection, the individual precursor ion populations are analyzed. In some cases, this analysis might involve additional rounds of ion isolation and manipulation (e.g., MSn, CID, ETD, etc.).