MALDI Sample Preparation via Liquid Bridge Separation

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Solution Overview

Problem

Current MALDI sample preparation methods for ionization are hindered by insoluble cell residues that impede matrix crystallization, requiring precise manual handling and being time-consuming, especially when dealing with resistant biological materials like yeasts.

Innovation Solution

A method involving a separate deposition site and sample site with liquid communication allows soluble analyte molecules to diffuse or be conveyed to the sample site, separating them from insoluble cell residues, enabling homogeneous matrix crystallization without interference.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If manual handling with inoculation swab is used to transfer biological material, then precise quantity control can be achieved, but the preparation process becomes time-consuming and requires high technician skill

Engineering Contradiction:
Improvequantity control precisionVSAvoidpreparation time
Core Design Contradiction:
Manufacturing precisionVSLoss of time

Solution Approach 1:

The sample preparation process is segmented into two distinct sites: a deposition site for applying biological material and a sample site for matrix crystallization. This segmentation allows automated deposition without requiring precise manual handling at the crystallization site, reducing both time and skill requirements while maintaining quantity control precision through the liquid communication bridge.

Inventive Principle:
Principle #1Segmentation

2Quantity of substance

If larger quantities of biological material are deposited to ensure sufficient analyte molecules, then detection sensitivity improves, but insoluble cell residues impede matrix crystallization

Engineering Contradiction:
Improveanalyte molecule quantityVSAvoidcrystal structure quality
Core Design Contradiction:
Quantity of substanceVSManufacturing precision

Solution Approach 1:

The harmful insoluble cell residues are extracted and left behind at the deposition site, while only the soluble analyte molecules are transferred through the liquid communication to the sample site. This allows larger quantities of biological material to be deposited without compromising crystal structure quality, as the residues remain separated from the crystallization process.

Inventive Principle:
Principle #2Taking out (Extraction)

3Manufacturing precision

If filtration or centrifugation is used to remove cell residues before sample preparation, then matrix crystallization quality improves, but the preparation process becomes very time-consuming

Engineering Contradiction:
Improvecrystal structure qualityVSAvoidpreparation time
Core Design Contradiction:
Manufacturing precisionVSLoss of time

Solution Approach 1:

The liquid communication bridge acts as an intermediary that selectively transfers soluble analyte molecules from the deposition site to the sample site while blocking insoluble cell residues. This eliminates the need for time-consuming filtration or centrifugation steps, as the separation function is performed passively by the liquid bridge interface during the transfer process.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 simplifies sample preparation by allowing larger quantities of analyte material to be used, reducing the need for precise handling, and ensuring uniform matrix distribution, leading to improved ionization yields and easier detection in mass spectrometry.

Implementation Method 1

allows soluble analyte molecules to diffuse or be conveyed to the sample site, separating them from insoluble cell residues

Methodology Applied
Scientific EffectDiffusion: Diffusion

Implementation Method 2

The matrix solution contains dissolved molecules of the matrix substance, which, as the drying process proceeds, form the crystals into which the analyte molecules are embedded

Methodology Applied
Scientific EffectEvaporation: Evaporation

Implementation Method 3

If the matrix crystal structure is exposed to pulses of laser radiation, it vaporises explosively and releases the embedded analyte molecules. Analyte molecules are also ionised during this very energetic ablation process

Methodology Applied
Scientific EffectLaser ablation: Laser Ablation

Data Source

PatentEP2466290B1Sample preparation for ionisation with matrix-assisted laser desorption
Publication Date: 2019.05.22 BRUKER DALTONIK GMBH
  • EP2466290B1 patent drawingFigure 1A~1F
  • EP2466290B1 patent drawingFigure 2A~2G
  • EP2466290B1 patent drawingFigure 3~6

AI summary

A simplified sample preparation on a sample support for ionisation with laser desorption (MALDI or LDCI, for example) is proposed, whereby a homogeneous crystallisation of the matrix material is possible, even if a large quantity of analyte material is deposited, serving as the source of the analyte molecules. The method includes depositing the analyte material onto a deposition site, providing a sample site which is intended as the substrate for a matrix crystal layer at a distance from the deposition site, and establishing a liquid communication between the deposition site and the sample site. The invention also relates to a device for the preparation of samples for ionisation with matrix-assisted laser desorption, and to a sample support.