Liquid Phase Matrix Ablation for Multiply Charged Ion Production

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Solution Overview

Problem

Current MALDI methods fail to produce desirable amounts of multiply charged ions, which limits their application in mass spectrometry, especially for large biomolecules like peptides, due to their inability to generate high charge states and being less suitable for samples with contaminants and additives.

Innovation Solution

A method involving a matrix composition with a non-volatile liquid component and a chromophore-absorbing matrix material, where the composition and analyte are deposited in intimate contact on a surface and ablated with a laser in the liquid phase, followed by passing the desorbed ions through a heated conduit to enhance multiply charged ion production.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If conventional MALDI methods are used with solid matrix/analyte composition, then the sample can be deposited and analyzed, but the production of multiply charged ions is insufficient

Engineering Contradiction:
Improveamount of multiply charged ionsVSAvoidionization efficiency
Core Design Contradiction:
Quantity of substanceVSEase of manufacture

Solution Approach 1:

The patent changes the physical state parameter of the matrix/analyte composition from solid to liquid phase during laser ablation. This parameter change enables efficient production of multiply charged ions while maintaining ease of sample deposition and analysis

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses a composite matrix composition comprising a matrix material and a non-volatile liquid component. This composite material enables the liquid phase ablation process that generates multiply charged ions, combining the benefits of MALDI with enhanced ionization capabilities

Inventive Principle:
Principle #40Composite materials

2Productivity

If laser fluence is increased to produce more ions, then ion yield increases, but analyte consumption increases

Engineering Contradiction:
Improveion yieldVSAvoidanalyte consumption
Core Design Contradiction:
ProductivityVSLoss of substance

Solution Approach 1:

The patent changes the phase parameter to liquid, which enables high ion yield at low laser fluence. The liquid phase allows for more efficient energy transfer and ion generation, reducing the need for high laser power and thereby minimizing analyte consumption

Inventive Principle:
Principle #35Parameter changes

3Quantity of substance

If conventional MALDI is used, then singly charged ions are produced, but multiply charged ions are not generated in desirable amounts

Engineering Contradiction:
Improvemultiply charged ionsVSAvoidreproducibility of ion production
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The composite matrix composition with non-volatile liquid component provides a stable liquid phase that consistently produces multiply charged ions. This composite material ensures reproducible ion production across multiple laser shots and samples

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The phase change to liquid state creates a more favorable environment for multiple protonation events, leading to consistent production of multiply charged ions with high reproducibility

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 method increases the number of multiply charged ions available for analysis, providing good reproducibility and prolonged ion yield with low laser fluence, minimizing analyte consumption and allowing flexibility in sample preparation, and is effective for large biomolecules like peptides and proteins.

Implementation Method 1

the matrix material comprises molecules which possess a chromophore which absorbs strongly in the UV or IR regions of the spectrum

Methodology Applied
Scientific EffectChromophore absorption: Absorption (EM radiation)

Implementation Method 2

ablating the composition and the analyte deposited on the surface with a laser to desorb multiply charged ions of analyte

Methodology Applied
Scientific EffectLaser ablation: Laser Ablation

Implementation Method 3

the matrix composition and analyte are ablated in the liquid phase

Methodology Applied
Scientific EffectAblation: Ablation

Implementation Method 4

passing the desorbed multiply charged ions through a heated conduit

Methodology Applied
Scientific EffectHeating: Heating

Data Source

PatentUS9552972B2Method for ion production
Publication Date: 2017.01.24 THE UNIV OF READING
  • US9552972B2 patent drawing
  • US9552972B2 patent drawing
  • US9552972B2 patent drawing

AI summary

A method for producing multiply charged ions is provided. In the method, a laser is used to ablate a sample comprising a matrix and an analyte. The sample is in the liquid form when it is ablated and the ions produced are passed through a heated conduit. The multiply charged ions produced may be used in mass spectrometry to measure the mass of the analyte.