MALDI Mass Spectrometry Ion Generation Temperature Control

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Solution Overview

Problem

The reproducibility of mass spectra in MALDI mass spectrometry is poor, limiting its industrial and scientific applicability for quantitative analysis, especially due to challenges in controlling ion generation temperatures and obtaining accurate calibration curves for analytes, particularly with high molecular weight materials like proteins and peptides.

Innovation Solution

A method is developed to control ion generation temperatures by selecting spectra with consistent early plume temperatures, allowing for reproducible fragmentation patterns and total ion counts, and using these conditions to measure equilibrium constants and obtain calibration curves for quantitative analysis, thereby improving the accuracy of analyte quantification.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional MALDI mass spectrometry is used without temperature control, then the analysis process is simple, but the reproducibility of mass spectra is poor

Engineering Contradiction:
Improvereproducibility of mass spectraVSAvoidcomplexity of temperature control system
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies parameter changes by controlling the ion generation temperature as a critical parameter. By maintaining consistent temperature conditions during ion generation and selecting spectra with matched temperatures, the method achieves reproducible mass spectra and enables quantitative analysis without requiring complex additional hardware systems.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent implements feedback control by measuring the temperature of ion generation and using this information to select or re-acquire spectra with consistent temperatures. This feedback mechanism ensures that only spectra meeting the temperature consistency criterion are used for quantitative analysis, thereby improving reproducibility.

Inventive Principle:
Principle #23Feedback

2Measurement precision

If quantitative analysis is performed without temperature control, then the analysis method is simple, but the accuracy of quantitative results is poor

Engineering Contradiction:
Improveaccuracy of quantitative analysisVSAvoidcomplexity of temperature measurement and control system
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent changes the approach from ignoring temperature to actively controlling and monitoring temperature as a critical parameter. By measuring ion generation temperature and using it as a selection criterion for spectra, the method achieves accurate quantitative analysis while avoiding overly complex control systems.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent performs preliminary temperature measurement and spectrum selection before quantitative analysis. By pre-screening spectra based on temperature consistency and selecting only those that meet the criterion, the method ensures accurate quantitative results without requiring complex real-time control during the analysis process.

Inventive Principle:
Principle #10Preliminary action

3Measurement precision

If traditional quantitative analysis methods are used, then isotopic labeling can be avoided, but calibration curves cannot be obtained accurately

Engineering Contradiction:
Improveaccuracy of calibration curvesVSAvoidcomplexity of temperature control for calibration
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent applies parameter changes by controlling temperature during calibration curve generation. By ensuring consistent ion generation temperatures across all calibration standards and analyte samples, the method produces accurate calibration curves that enable reliable quantitative analysis without requiring isotopic labeling.

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 reproducible quantitative analysis of analytes, even in complex mixtures, by maintaining consistent ion generation conditions, reducing the need for expensive isotopic labeling and simplifying sample preparation, and enhancing the precision of MALDI mass spectrometry.

Implementation Method 1

a method is developed to control ion generation temperatures by selecting spectra with consistent early plume temperatures

Methodology Applied
Scientific EffectPhotoionization: Photoionisation

Implementation Method 2

selecting spectra with consistent early plume temperatures

Methodology Applied
Scientific EffectEvaporation: Evaporation

Implementation Method 3

temperatures of an ion generation reaction are controlled to be the same with each other

Methodology Applied
Scientific EffectHeating: Heating

Data Source

PatentUS9646810B2Method for improving mass spectrum reproducibility and quantitative analysis method using same
Publication Date: 2017.05.09 ASTA
  • US9646810B2 patent drawing
  • US9646810B2 patent drawing
  • US9646810B2 patent drawing

AI summary

Methods are described for improving reproducibility of mass spectrum and quantitative analysis method using the same. More particularly, methods for improving reproducibility of a mass spectrum of a chemical compound, wherein temperatures of an ion generation reaction are controlled to be the same with each other, or wherein spectra of which temperature of ion generation reaction are the same with each other are selected from mass spectra of a chemical compound are described. In addition, methods for measuring an equilibrium constant of a proton transfer reaction between a matrix and an analyte at a certain temperature, for obtaining a calibration curve for quantitative analysis, and for quantitative analysis of an analyte by using mass spectra area described.