Etched MALDI Test Plates for Uniform Matrix Crystallization

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Solution Overview

Problem

Inconsistencies in the size and distribution of matrix particles on support surfaces in MALDI MS lead to variability in energy transfer and poor reproducibility of molecular spectra, hindering the clinical application of MALDI Mass Spectrometry Imaging.

Innovation Solution

The method involves etching the surface of solid supports to create uniform nucleation sites for MALDI matrix crystallization, ensuring a homogeneous distribution of matrix crystals with controlled thickness and size, and optionally forming an organic semiconductor layer to enhance energy transfer.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If matrix material is deposited on solid support surfaces without surface etching, then the deposition process is simple, but the distribution of matrix particles is inconsistent leading to poor reproducibility of spectra

Engineering Contradiction:
Improvehomogeneity of matrix crystal distributionVSAvoidcomplexity of surface preparation process
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The solid support surface is etched with a pattern of pits or cavities before matrix deposition. This preliminary action creates predetermined nucleation sites that control where matrix crystals will form, ensuring uniform distribution and consistent energy transfer during MALDI analysis.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The surface is modified locally by creating specific etched regions with different properties (pits, cavities, or patterned areas) compared to the surrounding flat surface. These localized modifications provide controlled nucleation sites that guide matrix crystal formation in specific locations, achieving homogeneous distribution.

Inventive Principle:
Principle #3Local quality

2Reliability

If matrix particles are allowed to crystallize freely on the support surface, then the crystallization process is simple, but the crystal size and distribution vary leading to site-to-site variability in energy transfer

Engineering Contradiction:
Improvereproducibility of MALDI spectraVSAvoidease of matrix deposition
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The solid support surface is etched to create a porous or pitted structure with controlled depth and distribution. These porous features act as nucleation sites that control matrix crystal size and distribution, ensuring consistent energy transfer and improving spectral reproducibility while maintaining a relatively simple deposition process.

Inventive Principle:
Principle #31Porous materials

Solution Approach 2:

The surface is pre-modified with etched patterns before matrix deposition. This preliminary structuring of the surface provides controlled nucleation sites that guide crystal formation, ensuring uniform crystal size and distribution without complicating the actual matrix deposition step.

Inventive Principle:
Principle #10Preliminary action

3Manufacturing precision

If the solid support surface is etched to create uniform nucleation sites, then matrix crystal distribution becomes homogeneous, but the surface preparation process becomes more complex

Engineering Contradiction:
Improveuniformity of matrix crystal sizeVSAvoidcomplexity of etching process
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The solid support surface is etched with a pattern of pits or cavities before matrix deposition. This preliminary action creates predetermined nucleation sites that control where matrix crystals will form, ensuring uniform distribution and consistent energy transfer during MALDI analysis.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The etching process parameters (depth, pattern density, geometry) are optimized to create the desired nucleation site characteristics. By controlling these parameters, uniform crystal size and distribution are achieved while managing the complexity of the etching process itself.

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 results in more reproducible and accurate molecular spectra, improving the reliability of MALDI MS for diagnostic applications by reducing site-to-site variability and enhancing the representation of molecular distributions in tissues.

Implementation Method 1

etching the surface of solid supports to provide sites for crystal nucleation

Methodology Applied
Scientific EffectCrystallization: Crystallisation

Implementation Method 2

etching the surface of solid supports to provide sites for crystal nucleation

Methodology Applied
Scientific EffectNucleation: Nucleation

Implementation Method 3

a photon-absorbing matrix (usually a crystalline organic acid)... When exposed to pulses of laser light, the matrix transfers energy to molecules in the sample

Methodology Applied
Scientific EffectAbsorption (EM radiation): Absorption (EM radiation)

Implementation Method 4

the matrix transfers energy to molecules in the sample, thereby promoting their ionization and desorption

Methodology Applied
Scientific EffectIonization: Ionisation

Implementation Method 5

the matrix transfers energy to molecules in the sample, thereby promoting their ionization and desorption

Methodology Applied
Scientific EffectDesorption: Desorption

Implementation Method 6

optionally forming an organic semiconductor layer to enhance energy transfer

Methodology Applied
Scientific EffectPhotoconductivity: Photoconductivity

Data Source

PatentUS9455130B2Preparation of test plates for matrix assisted laser desorption ionization
Publication Date: 2016.09.27 THE BRIGHAM & WOMEN S HOSPITAL INC

AI summary

The present invention is directed, sample test plates that can be used in matrix assisted laser desorption ionization. These plates have an etched surface and a layer of MALDI matrix material. The invention also includes methods for making these sample test plates and to methods for using the plates in the MS imaging of cell and tissue samples.