FTMS Collision Cross-Section Measurement via Pressure Modulation

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Solution Overview

Problem

Existing methods for determining collision cross-sections (CCS) in Fourier transform mass spectrometry (FTMS) are limited by the need for ion isolation, leading to unreliable measurements at lower ion intensities and inability to perform online determination over wide mass ranges or in parallel with m/z determination.

Innovation Solution

The method involves using signal-to-noise ratio (SNR) and m/z-dependent corrections to extrapolate signal resolutions from low SNR values, tracking peak widths across elution profiles, and varying gas pressure to improve the accuracy and precision of CCS measurements, allowing for online determination of decay constants and CCS values.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If ion isolation is performed to achieve sufficiently high intensity for reliable peak width determination, then measurement precision of decay constant improves, but device complexity and measurement time increase, and parallel determination with m/z is lost

Engineering Contradiction:
Improvedecay constant determination accuracyVSAvoidmeasurement throughput
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent changes the parameter of gas pressure in the mass analyzer to control collision rates. By varying pressure, the system can obtain reliable decay constant measurements without requiring ion isolation, thus maintaining high throughput while achieving sufficient measurement precision through pressure-dependent collision frequency modulation

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces gas pressure as an intermediary parameter that mediates between ion intensity and measurement precision. By using pressure-controlled collisions as a mediator, the system can determine decay constants from lower intensity signals that would otherwise be insufficient, enabling parallel determination with m/z measurement

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If ion isolation is used to ensure high signal intensity, then decay rate measurement reliability improves, but the ability to determine CCS over wide mass ranges online is lost

Engineering Contradiction:
Improvesignal decay measurement reliabilityVSAvoidmass range coverage
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent uses gas pressure as a controllable parameter to enhance signal decay effects. By adjusting pressure to increase collision frequency, reliable decay measurements can be obtained even for low-intensity ions across wide mass ranges, eliminating the need for ion isolation and enabling online CCS determination for diverse mass ranges simultaneously

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent dynamically adjusts gas pressure during analysis to optimize collision rates for different mass ranges. This dynamic parameter control allows the system to maintain measurement reliability across varying ion intensities and mass ranges without requiring static ion isolation procedures

Inventive Principle:
Principle #15Dynamics

3Adaptability or versatility

If lower ion intensities are analyzed to cover wide mass ranges, then adaptability improves, but measurement precision deteriorates due to greater defocusing effects

Engineering Contradiction:
Improvemass range coverageVSAvoidsignal decay measurement accuracy
Core Design Contradiction:
Adaptability or versatilityVSMeasurement precision

Solution Approach 1:

The patent compensates for defocusing effects in low-intensity ions by introducing pressure-controlled collisions. The increased collision frequency at elevated pressure creates sufficient signal decay that can be measured reliably even when space charge defocusing is present, thereby maintaining measurement precision across wide mass ranges without ion isolation

Inventive Principle:
Principle #35Parameter changes

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 accurate and precise measurement of CCS values across wide mass ranges, improving the dynamic range and accuracy of FTMS, and facilitating quality control of mass peaks.

Implementation Method 1

Characteristics of the ions' periodic motion, such as one or more of intensities, phases, frequencies (i.e. m/z), decay constants, may be determined for multiple ion species simultaneously within the set of ions

Methodology Applied
Scientific EffectFourier transform:

Implementation Method 2

ions with higher CCS are expected to collide with background gas more frequently and hence the image signals provided by such ions are expected to decay more rapidly

Methodology Applied
Scientific EffectIon-molecule collision:

Data Source

PatentUS20230136166A1Method for Determining a Measure of a Rate of Decay and Mass Spectrometry System
Publication Date: 2023.05.04 THERMO FISHER SCI BREMEN
  • US20230136166A1 patent drawing
  • US20230136166A1 patent drawing
  • US20230136166A1 patent drawing

AI summary

Methods and systems for determining a measure of a rate of decay of an ion sample. Specifically, the present disclosure provides methods and apparatus for determining decay constants and cross-section measurements in parallel to mass measurement and decay time correction. The disclosure particularly relates to methods and apparatus for performing Fourier transform mass spectrometry (FTMS).