TOF-MS Mass Accuracy Correction via FTMS Reference

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Solution Overview

Problem

Time-of-flight mass spectrometers (TOF-MS) experience inaccuracies in mass accuracy due to thermal drift, which affects the calibration function linking flight times to mass-to-charge (m/z) ratios, as ambient temperature variations cause shifts in mechanical and electronic components.

Innovation Solution

A method involving a combination of Time of Flight (TOF) and Fourier Transform Mass Spectrometers (FTMS) is used, where calibrant ions are analyzed by both instruments to determine temperature correction factors, allowing for calibration of the TOF-MS to account for temperature changes, thereby maintaining mass accuracy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If temperature compensation methods such as material mixing, air flow mechanisms, or sensor-based mathematical models are used to maintain calibration accuracy, then mass measurement stability improves, but device complexity increases

Engineering Contradiction:

Improvemass measurement stabilityVSAvoidsystem complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent introduces an FTMS as an intermediary reference instrument with temperature-insensitive mass measurements. The FTMS data serves as a mediator to derive temperature correction factors that are then applied to the TOF-MS calibration, avoiding direct complex temperature compensation mechanisms in the TOF-MS itself

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces physical/mechanical temperature compensation methods (such as air flow mechanisms or mechanical expansion compensation) with a data-processing-based approach using FTMS reference measurements and mathematical correction factors

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Measurement precision

If multiple sensors and mathematical models are employed to measure temperature and strain for correction, then mass accuracy under temperature variation improves, but ease of operation deteriorates

Engineering Contradiction:

Improvemass accuracyVSAvoidoperational simplicity

Core Design Contradiction:

Measurement precisionVSEase of operation

Solution Approach 1:

The system performs self-calibration by automatically comparing TOF-MS measurements with FTMS reference measurements and deriving correction factors without requiring manual intervention for temperature monitoring or calibration adjustments

Inventive Principle:

Principle #25Self-service

3Reliability

If predetermined thermal expansion correction factors are used to adjust flight path length, then mass measurement stability improves, but adaptability to unknown temperature profiles deteriorates

Engineering Contradiction:

Improvemass measurement stabilityVSAvoidadaptability to temperature changes

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent implements a feedback mechanism where actual FTMS reference measurements continuously inform the correction factor calculation, allowing the system to adapt to real temperature conditions rather than relying on predetermined theoretical correction factors

Inventive Principle:

Principle #23Feedback

Solution Approach 2:

The patent dynamically adjusts the calibration parameters (mass-to-time relationship) based on actual measured temperature effects captured through FTMS reference measurements, rather than using fixed predetermined correction factors

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 effectively stabilizes the mass accuracy of TOF-MS by using temperature-independent FTMS data to correct for thermal shifts in TOF-MS data, ensuring precise mass-to-charge ratio calculations despite temperature fluctuations.

Implementation Method 1

In time-of-flight (TOF) mass spectrometry, flight times of ions are measured to determine mass-to-charge (m/z) ratios. As is well known, the time of flight of an ion is proportional to the square root of its mass to charge ratio.

Methodology Applied

Scientific EffectTime of flight: Time of Flight

Implementation Method 2

The ambient temperature of a mass spectrometer can vary by more than 10 degrees Celsius during use, which leads to thermal expansion of the mechanical parts and thermally induced drift of the electronic components (voltage supplies).

Methodology Applied

Scientific EffectThermal expansion: Thermal Expansion

Data Source

PatentUS10593525B2Mass error correction due to thermal drift in a time of flight mass spectrometer

Publication Date: 2020.03.17 THERMO FISHER SCI BREMEN

AI summary

A method of calibrating a TOF-MS mass spectrum, to account for temperature changes, is disclosed. Ions are introduced into a Fourier Transform Mass Spectrometer and their mass to charge ratios are determined. Ions, including calibrant ions, are also introduced into a time of flight mass spectrometer and the mass to charge ratios of the calibrant ions at least are also determined. Specific peaks representative of calibrant ions are selected and matched between the TOF MS and FTMS spectra. The relative position of matched peaks in each spectrum is then used to determine a temperature correction factor for the TOF MS data, based upon the relative independence of the FTMS spectrum with respect to temperature.