Two-Dimensional Sample Separation for MALDI Mass Accuracy

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Solution Overview

Problem

Conventional chromatographic separation methods for complex biological samples are time-consuming and not ideally suited for subsequent Matrix Assisted Laser Desorption Ionisation (MALDI) mass spectrometry analysis, leading to mass spectral peak broadening and degradation of mass accuracy.

Innovation Solution

A method involving mechanical, hydrodynamic, and/or aerodynamic means for depositing and separating samples on a non-porous, optimized target surface in two dimensions, allowing for rapid pseudo-separation and subsequent MALDI mass spectrometry imaging with improved mass accuracy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional chromatographic separation methods are used, then separation of complex biological samples is achieved, but the process is time-consuming and mass spectral peak broadening occurs

Engineering Contradiction:

Improvemass spectral peak accuracyVSAvoidsample preparation time

Core Design Contradiction:

Measurement precisionVSLoss of time

Solution Approach 1:

The patent replaces conventional chromatographic separation (mechanical/chemical process) with direct deposition onto a mechanically agitated target surface. The mechanical agitation of the target creates rapid pseudo-separation based on analyte volatility and adsorption characteristics, eliminating the need for time-consuming chromatographic columns and reducing mass spectral peak broadening.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent applies matrix coating and sample deposition in advance onto the target surface before analysis. The mechanical agitation during deposition pre-separates analytes based on their volatility and adsorption properties, creating a spatial distribution that enables rapid analysis without subsequent chromatographic separation steps.

Inventive Principle:

Principle #10Preliminary action

2Measurement precision

If conventional chromatographic substrates are used, then separation is achieved, but the surface is not ideally suited for subsequent MALDI mass spectrometry analysis

Engineering Contradiction:

Improvemass spectrometry analysis qualityVSAvoidchromatographic substrate complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent merges the separation function and the mass spectrometry target function into a single integrated system. The target surface serves both as the separation medium (through mechanical agitation) and as the MALDI analysis substrate, eliminating the need for complex chromatographic substrates and their associated complexity.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The patent changes the operational parameters of the target surface by applying mechanical agitation during sample deposition. This creates a dynamic separation environment that produces analyte distributions optimized for MALDI mass spectrometry, transforming the target from a static substrate to an active separation medium with ideal surface properties for mass spectrometry.

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 fast, simple, and accurate two-dimensional separation of complex biological samples on a surface optimized for MALDI mass spectrometry, reducing preparation time and enhancing analysis specificity without complex procedures.

Implementation Method 1

separating the sample on the target surface according to a first physico-chemical property in a first dimension and according to a second physico-chemical property in a second dimension by mechanical, hydrodynamic and/or aerodynamic means

Methodology Applied

Scientific EffectMechanical separation:

Implementation Method 2

Methodology Applied

Scientific EffectHydrodynamic separation:

Implementation Method 3

Methodology Applied

Scientific EffectAerodynamic separation:

Implementation Method 4

ionising and mass analysing multiple separate regions of the sample so as to generate an ion map

Methodology Applied

Scientific EffectIonisation: Ionisation

Data Source

PatentUS10032612B2Two-dimensional separation and imaging technique for the rapid analysis of biological samples

Publication Date: 2018.07.24 MICROMASS UK LTD

AI summary

A method of ion mapping is disclosed comprising depositing a sample onto a target surface and separating the sample on the target surface according to a first physico-chemical property in a first dimension and according to a second physico-chemical property in a second dimension. The method further comprises ionising and mass analysing multiple separate regions of the sample so as to generate an ion map of at least a portion of the sample deposited upon the target surface. The sample is deposited onto and separated on the target surface by mechanical, hydrodynamic and/or aerodynamic means.