REIMS Ionization Using Matrix Dilution for Lipid-Rich Tissue Analysis

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Solution Overview

Problem

Rapid evaporative ionization mass spectrometry (REIMS) techniques face low ionization yields due to strong intermolecular bonds between analyte molecules, particularly when analyzing tissues with high neutral lipid content like adipose or breast tissue, and are hindered by electrosurgical diathermy coagulation mode and sample carryover issues.

Innovation Solution

Diluting or dissolving the analyte in a matrix before collision with a surface, which reduces intermolecular bonding, facilitates ionic dissociation, and enhances ionization by fragmenting into smaller droplets, using methods like laser irradiation, ultrasonic energy, or glow discharge for dissociation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If direct collision of aerosol particles with collision surface is used, then ionization is enhanced, but ionization yield remains relatively low due to strong intermolecular bonds between analyte molecules

Engineering Contradiction:
Improveionization efficiencyVSAvoidionization yield
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent applies preliminary action by dissolving the analyte in a matrix compound before collision with the collision surface. This pre-treatment step reduces intermolecular bonding between analyte molecules, making them more susceptible to ionization upon collision. The matrix compound facilitates ionic dissociation before the actual ionization event occurs at the collision surface.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The matrix compound acts as an intermediary substance between the analyte and the collision surface. It mediates the ionization process by forming a solution with the analyte that has reduced intermolecular bonds, thereby facilitating more efficient ionization when the solution collides with the collision surface. The matrix enables the analyte to be more easily ionized without direct contact with the collision surface.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If electrospray post-ionisation is used to enhance ion yield, then ionization is improved, but patient safety is compromised due to high voltages involved

Engineering Contradiction:
Improveionization yieldVSAvoidpatient safety
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent replaces the electrical field-based electrospray ionization method with a mechanical collision-based ionization method. Instead of using high voltage electrical fields to ionize the analyte, the patent uses physical collision of the analyte-matrix solution with a collision surface to achieve ionization. This substitution eliminates the safety hazards associated with high voltages while maintaining effective ionization.

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

3Measurement precision

If REIMS analysis is performed on tissues with high neutral lipid content, then tissue identification is attempted, but ionization is suppressed due to strong intermolecular bonds in lipids

Engineering Contradiction:
Improvetissue identification accuracyVSAvoidionization efficiency
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent changes the physical-chemical parameters of the analyte by dissolving it in a matrix compound. This parameter change reduces the strength of intermolecular bonds between lipid molecules, making them more amenable to ionization. The matrix compound alters the molecular environment of the lipids, facilitating ionic dissociation and improving ionization efficiency for tissues with high neutral lipid content.

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 significantly increases the ionization efficiency by ensuring more analyte molecules are ionized, improving the detection of tissues with high lipid content and reducing interference from electrosurgical procedures.

Implementation Method 1

supplying a matrix compound to the analyte such that the analyte is diluted or dissolved in, or forms first clusters with the matrix; and colliding the first clusters or first droplets of the diluted or dissolved analyte with a collision surface

Methodology Applied
Scientific EffectIonic dissociation: Ionisation

Implementation Method 2

fragmenting into smaller droplets, using methods like laser irradiation

Methodology Applied
Scientific EffectLaser ablation: Laser Ablation

Implementation Method 3

ultrasonic energy, or glow discharge for dissociation

Methodology Applied
Scientific EffectUltrasonic vibration: Ultrasonic Vibration

Implementation Method 4

laser irradiation, ultrasonic energy, or glow discharge for dissociation

Methodology Applied
Scientific EffectGlow discharge: Electric Glow Discharge

Implementation Method 5

a mass spectrometric signal is obtained by subjecting a substrate to alternating electric current at radiofrequency which causes localized Joule-heating and the disruption of cells along with desorption of charged and neutral particles

Methodology Applied
Scientific EffectJoule heating: Joule Heating

Data Source

PatentEP4174906A1Improved ionisation of gaseous samples
Publication Date: 2023.05.03 MICROMASS UK LTD
  • EP4174906A1 patent drawingFigure 1
  • EP4174906A1 patent drawingFigure 2
  • EP4174906A1 patent drawingFigure 3

AI summary

Method of mass spectrometry or ion mobility spectrometry comprising the steps of providing an analyte; diluting the analyte by a matrix thereby forming droplets of diluted analyte, dissolving the analyte by a matrix thereby forming droplets of dissolved analyte, or forming cluster ions with analyte and matrix; fragmenting or disintegrating these droplets or clusters; wherein the fragmenting or disintegration is by laser irradiation, ultrasonic energy, glow discharge or photoionization.