Liquid Extraction MALDI Ion Source for Salt-Tolerant Mass Spectrometry

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Solution Overview

Problem

Current ionization techniques, such as Electrospray Ionization, face limitations in sensitivity to salts and ionization suppression effects, and do not effectively release analyte ions or plumes from a liquid junction, limiting their applicability in mass spectrometry.

Innovation Solution

A Matrix Assisted Laser Desorption Ionization (MALDI) ion source is developed, which supplies a liquid flow to form a junction on a sample surface, extracting analytes into the junction, and uses a laser to desorb analyte ions or plumes for analysis by a mass spectrometer, offering improved sensitivity and tolerance to salts compared to Electrospray Ionization.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If Electrospray Ionization is used to ionize analytes from a liquid junction, then ionization can be achieved, but sensitivity to salts and ionization suppression effects worsen

Engineering Contradiction:
Improveionization sensitivityVSAvoidsalt interference and ionization suppression
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent replaces the electrical field-based Electrospray Ionization mechanism with a laser-based MALDI mechanism. Instead of using high voltage to generate ions from the liquid junction, a laser beam is used to desorb and ionize analytes directly from the liquid junction, thereby avoiding the ionization suppression effects that plague ESI in the presence of salts

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

Solution Approach 2:

The patent changes the fundamental ionization parameter from electrical field strength (in ESI) to laser energy density (in MALDI). This parameter change allows ionization to occur through a different physical mechanism that is less sensitive to salt interference, as the laser directly ablates and ionizes the analyte molecules rather than relying on electrospray processes that are suppressed by ionic strength

Inventive Principle:
Principle #35Parameter changes

2Quantity of substance

If a laser beam is applied to the liquid junction, then analyte dissolution is improved, but analyte ions or plume release is not achieved

Engineering Contradiction:
Improveanalyte dissolutionVSAvoidion release efficiency
Core Design Contradiction:
Quantity of substanceVSProductivity

Solution Approach 1:

The patent employs pulsed laser irradiation rather than continuous irradiation. The periodic pulsed action allows the laser to first dissolve/extract analytes into the liquid junction during one pulse, then subsequently desorb and release ionized analytes in a following pulse, thereby achieving both dissolution and ion release through temporal separation of these functions

Inventive Principle:
Principle #19Periodic action

Solution Approach 2:

The patent utilizes phase transitions induced by laser heating. The laser beam causes rapid heating and phase change of the liquid junction material, transforming it from a liquid state (favorable for dissolution) to a vaporized/plasma state (favorable for ion release and desorption). This phase transition mechanism enables the laser to perform both dissolution enhancement and ion plume generation

Inventive Principle:
Principle #36Phase transitions

3Measurement precision

If liquid extraction is used to analyze samples, then spatial resolution is achieved, but data processing time increases for fast eluting samples

Engineering Contradiction:
Improvespatial resolutionVSAvoiddata processing time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The MALDI ion source performs preliminary ionization and desorption of analytes directly from the liquid junction at the point of extraction. This preliminary action occurs before the analytes enter the mass spectrometer, allowing fast eluting samples to be captured and ionized immediately rather than requiring extended data collection and processing times

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent replaces the time-consuming ESI ionization process with rapid laser-based MALDI ionization. The laser pulse duration (typically nanoseconds) is much shorter than the data processing time required for ESI of fast eluting samples, thereby enabling spatially resolved analysis without sacrificing temporal resolution

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

The MALDI ion source provides sensitive ionization with reduced salt interference, enabling complementary information and efficient data processing, particularly suited for analyzing samples that elute quickly, and allows for the analysis of high molecular weight samples without vacuum requirements.

Implementation Method 1

a first device arranged and adapted to supply a flow of liquid on to the surface of a target or a sample to be analysed so that the liquid forms a liquid junction on the surface of the target or the sample to be analysed and wherein analyte molecules to be ionised are extracted into the liquid junction

Methodology Applied
Scientific EffectExtraction: Liquid-Liquid Extraction

Implementation Method 2

a laser source arranged and adapted to emit a laser beam, wherein the laser beam is arranged and adapted to cause analyte ions or an analyte plume to be released or desorbed from the liquid junction

Methodology Applied
Scientific EffectLaser desorption: Laser Ablation

Implementation Method 3

Matrix Assisted Laser Desorption Ionisation technique which supplies a liquid flow to form a junction on a sample surface, extracting analytes into the junction, and uses a laser to desorb analyte ions or plumes

Methodology Applied
Scientific EffectMatrix assisted laser desorption ionization: Photoionisation

Data Source

PatentUS10090144B2Liquid extraction matrix assisted laser desorption ionisation ion source
Publication Date: 2018.10.02 MICROMASS UK LTD
  • US10090144B2 patent drawing
  • US10090144B2 patent drawing

AI summary

A Matrix Assisted Laser Desorption Ionization (“MALDI”) ion source is disclosed comprising a first device arranged and adapted to supply a flow of liquid on to the surface of a target or a sample to be analyzed so that the liquid forms a liquid junction on the surface of the target or the sample to be analyzed and wherein analyte molecules to be ionized are extracted into the liquid junction, and a laser source emits a laser beam which causes analyte ions or an analyte plume to be released or desorbed from the liquid junction.