MALDI-TOF Mass Spectrometer Variable Delay Extraction

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Solution Overview

Problem

Time-of-flight mass spectrometers face challenges in maintaining spectral resolution and mass accuracy due to ions having different kinetic energies and being accelerated from various points in space, which degrades the spectral quality and mass accuracy, especially in MALDI-TOF systems.

Innovation Solution

Implementing a DE-MALDI-TOF MS system with a variable delay time module that automatically adjusts the delay times between ionization and acceleration, allowing for successive varying delay times to focus on different mass signals, thereby improving spectral resolution and mass accuracy by generating composite or superimposed spectra.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If delayed extraction is used to improve spectral resolution, then mass accuracy improves, but signal acquisition time increases and requires prior tuning

Engineering Contradiction:
Improvemass accuracyVSAvoidsignal acquisition time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The system dynamically adjusts the delay time between laser ionization and extraction pulse application based on the mass-to-charge ratio range being analyzed. The controller automatically varies the delay time to optimize focusing for different mass ranges, eliminating the need for manual prior tuning while maintaining high mass accuracy across broader mass ranges.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The system changes the extraction delay time parameter automatically depending on the detected ion mass range. By adjusting this critical parameter dynamically, the system optimizes spectral resolution and mass accuracy for different analytes without requiring manual intervention or prior knowledge of the sample composition.

Inventive Principle:
Principle #35Parameter changes

2Ease of operation

If fixed delay time is used for extraction, then system operation is simple, but spectral resolution degrades for ions with different kinetic energies

Engineering Contradiction:
Improvesystem operation simplicityVSAvoidspectral resolution
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The mass spectrometer performs self-optimization by automatically adjusting the extraction delay time based on real-time detection of ion arrival times and mass ranges. The controller monitors the spectral quality and autonomously varies the delay time to maintain optimal spectral resolution, eliminating the need for operator intervention while preserving ease of operation.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The system implements feedback control where the controller continuously monitors ion detection data and adjusts the extraction delay time accordingly. This closed-loop control ensures that spectral resolution is optimized automatically for different ion populations without requiring manual tuning, maintaining both simplicity and precision.

Inventive Principle:
Principle #23Feedback

3Measurement precision

If manual tuning is required to optimize focus mass, then measurement precision can be maximized, but productivity decreases due to additional preparation time

Engineering Contradiction:
Improvefocus mass accuracyVSAvoidsignal acquisition throughput
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The system performs preliminary automatic calibration and delay time optimization routines that prepare the instrument for optimal performance before sample analysis. This preliminary automated setup eliminates the need for manual tuning during actual signal acquisition, maximizing both focus mass accuracy and productivity by reducing preparation time.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The system replaces manual mechanical adjustment mechanisms with automated electronic control of the extraction delay time. The controller electronically adjusts timing parameters based on detected ion characteristics, substituting manual tuning operations with automated electronic optimization, thereby increasing throughput while maintaining precision.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

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 spectral resolution and mass accuracy over a broader range, enabling the identification of microorganisms and other sample constituents with improved resolving power and reduced signal acquisition time, without the need for prior tuning of the mass spectrometer.

Implementation Method 1

Mass spectrometers are devices which vaporize and ionize a sample

Methodology Applied
Scientific EffectIonization: Ionisation

Implementation Method 2

determine the mass to charge ratios of the collection of ions formed by the amount of time required for that ion to be transmitted under the influence of pulsed electric fields

Methodology Applied
Scientific EffectElectrical acceleration: Electric Field

Implementation Method 3

the mass to charge ratio of an ion is determined by the amount of time required for that ion to be transmitted under the influence of pulsed electric fields from the ion source to a detector

Methodology Applied
Scientific EffectTime of flight: Time of Flight

Data Source

PatentUS10910209B2MALDI-TOF mass spectrometers with delay time variations and related methods
Publication Date: 2021.02.02 BIOMERIEUX INC
  • US10910209B2 patent drawing
  • US10910209B2 patent drawing
  • US10910209B2 patent drawing

AI summary

MALDI-TOF MS systems have solid state lasers and successive and varied delay times between ionization and acceleration (e.g. extraction) to change focus masses during a single sample signal acquisition without requiring tuning of the MS by a user. The (successive) different delay times can change by 1 ns to about 500 ns, and can be in a range that is between 1-2500 nanoseconds.