Inkjet-Dispensed 2,5-Dihydroxybenzoic Acid for MALDI Crystal Uniformity

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Solution Overview

Problem

Current MALDI mass spectrometry methods face challenges in achieving uniform crystal formation and high sensitivity, particularly with matrices like 2,5-dihydroxybenzoic acid, which affects the quality of mass spectrometric imaging and the ability to conduct multi-stage MS analysis, especially for protein analysis using instruments like AXIMA-CFRplus.

Innovation Solution

A method involving the preparation of a 2,5-dihydroxybenzoic acid matrix solution at a concentration of 40 mg/mL to saturated, dispensed using an inkjet mechanism with a pitch of 150 to 175 µm on a conductive support, allowing for uniform microcrystal formation and effective ionization, suitable for both frozen and paraffin-embedded biological samples.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If conventional matrix solutions are used for MALDI mass spectrometry, then the analysis can be performed, but uniform crystal formation is difficult to achieve and sensitivity is reduced

Engineering Contradiction:
Improvecrystal formation uniformityVSAvoidionization sensitivity
Core Design Contradiction:
Manufacturing precisionVSReliability

Solution Approach 1:

The patent changes the concentration parameter of the matrix solution from conventional low concentrations to high concentration (saturated or near-saturated). This parameter change enables uniform microcrystal formation while maintaining high ionization sensitivity, resolving the contradiction between crystal uniformity and sensitivity.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent replaces conventional dispensing methods with an inkjet mechanism that can precisely control the deposition of high-concentration matrix solution. This substitution enables uniform distribution of the concentrated matrix, achieving both uniform crystal formation and high sensitivity.

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

2Manufacturing precision

If high-concentration matrix solution is dispensed, then uniform microcrystal formation is achieved, but the complexity of the dispensing process increases

Engineering Contradiction:
Improvemicrocrystal uniformityVSAvoiddispensing process complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent employs an inkjet mechanism that automatically controls the dispensing process with high precision. This automated system replaces manual or less precise dispensing methods, achieving uniform microcrystal formation from high-concentration solution while managing the process complexity through automation.

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

Solution Approach 2:

The high-concentration matrix solution inherently promotes uniform crystal formation through its saturation state, reducing the need for complex external control mechanisms. The solution itself contributes to the uniformity, simplifying the overall process despite the concentrated formulation.

Inventive Principle:
Principle #25Self-service

3Adaptability or versatility

If conventional matrixes are used for protein analysis, then the analysis can be performed, but multi-stage MS analysis capability is limited

Engineering Contradiction:
Improvemulti-stage MS capabilityVSAvoidprotein analysis performance
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The patent uses 2,5-dihydroxybenzoic acid at high concentration, which provides superior ionization efficiency and spectral quality. This enables reliable multi-stage MS analysis by providing sufficient signal intensity and resolution, thereby achieving both versatility and reliability in protein analysis.

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 high-quality mass spectrometric imaging with stable and effective ionization of biological molecules, allowing for precise positional information and successful multi-stage MS analysis, enhancing the sensitivity and reproducibility of protein analysis.

Implementation Method 1

dispensing the matrix solution to a sample to be analyzed by using an inkjet mechanism, to crystallize the 2,5-dihydroxybenzoic acid

Methodology Applied
Scientific EffectCrystallisation: Crystallisation

Implementation Method 2

matrix-assisted laser desorption/ionization mass spectrometry

Methodology Applied
Scientific EffectIonisation: Ionisation

Implementation Method 3

matrix-assisted laser desorption/ionization mass spectrometry

Methodology Applied
Scientific EffectLaser: Laser

Data Source

PatentEP2063265B1Method of preparing sample for matrix-assisted laser desorption ionization mass spectrometry and matrix-assisted laser desorption ionization mass spectrometry
Publication Date: 2022.12.14 SHIMADZU CORP
  • EP2063265B1 patent drawingFigure 1(a)~1(b)
  • EP2063265B1 patent drawingFigure 2(a)~2(b)
  • EP2063265B1 patent drawingFigure 3~4

AI summary

It is intended to provide a method of preparing sample for matrix-assisted laser desorption/ionization mass spectrometry using a matrix capable of generating preferred crystals that cause effective ionization of a molecule to be measured. A method of preparing a sample for matrix-assisted laser desorption/ionization mass spectrometry comprising the steps of: preparing a solution of 2,5-dihydroxybenzoic acid of 40 mg/mL to saturated concentration as a matrix solution; and dispensing the matrix solution to a sample to be analyzed by using an inkjet mechanism, to crystallize the 2,5-dihydroxybenzoic acid.