Matrix Solution Crystallization via Mechanical Vibration

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Solution Overview

Problem

The preparation of matrix substances like 2,5-dihydroxyacetophenone (DHAP) for mass spectrometric analyses is labor-intensive and time-consuming, making it difficult to achieve uniform crystallization on sample supports, which hinders efficient matrix-assisted ionization in MALDI techniques.

Innovation Solution

A method involving the combination of small solid bodies with a matrix solution in microvessels, shaken to initiate crystallization, allowing for the transfer of a turbid solution onto sample supports for uniform crystal layer formation, suitable for automated preparation of multiple samples.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If manual pipetting and scraping method is used to initiate crystallization, then uniform crystal layer can be formed, but the process is labor-intensive and time-consuming

Engineering Contradiction:
Improveuniformity of crystal layerVSAvoidpreparation speed
Core Design Contradiction:
Manufacturing precisionVSProductivity

Solution Approach 1:

The patent applies mechanical vibration through a vortex mixer to initiate and promote uniform crystallization of matrix material in the sample solution. The vibration energy causes the solution to become turbid uniformly throughout, replacing the manual scraping method and enabling automated high-throughput sample preparation while maintaining crystal layer uniformity.

Inventive Principle:
Principle #18Mechanical vibration

2Manufacturing precision

If manual pipetting method is used to apply solution to sample support, then crystal layer can be formed, but the process cannot be automated

Engineering Contradiction:
Improvecrystal layer formationVSAvoidautomatability of preparation
Core Design Contradiction:
Manufacturing precisionVSExtent of automation

Solution Approach 1:

The vortex mixer provides mechanical vibration that can be easily integrated into automated liquid handling systems. The vibration-induced crystallization is a robust process that does not require manual skill, allowing pipetting robots to automatically dispense the turbid solution onto sample supports while maintaining consistent crystal layer formation across hundreds of samples.

Inventive Principle:
Principle #18Mechanical vibration

3Measurement precision

If DHAP matrix material is used for mass spectrometric analysis, then high mass resolution and sensitivity are achieved, but uniform crystallization is difficult to obtain

Engineering Contradiction:
Improvemass resolutionVSAvoiduniformity of crystal deposition
Core Design Contradiction:
Measurement precisionVSManufacturing precision

Solution Approach 1:

The vortex mixer applies mechanical vibration to the DHAP-containing sample solution, which promotes uniform nucleation and crystallization throughout the solution volume. This vibration-induced crystallization prevents the formation of irregular crusts at droplet edges and ensures uniform crystal deposition on the sample support, thereby preserving the high mass resolution and sensitivity characteristics of DHAP.

Inventive Principle:
Principle #18Mechanical vibration

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 method enables faster and more uniform homogenization of matrix solutions, facilitating the use of DHAP and other matrix materials by automating the preparation process, resulting in high mass resolution and efficient ionization for MALDI analyses.

Implementation Method 1

The solution with the bodies is shaken or otherwise agitated for a predetermined length of time, and a suitable quantity of the shaken or agitated solution is transferred onto a mass spectrometric sample support

Methodology Applied
Scientific EffectCrystallization: Crystallisation

Implementation Method 2

rapidly drawing it in and out with a pipette for several minutes until the solution becomes turbid because of a large number of crystal nuclei

Methodology Applied
Scientific EffectNucleation: Nucleation

Implementation Method 3

It is advantageous here if the solvent, such as ethanol, evaporates in order to increase the concentration of the matrix material

Methodology Applied
Scientific EffectEvaporation: Evaporation

Implementation Method 4

A pipette can then be used to apply approximately one to two microliters of the turbid solution to a sample support, for example at an anchor spot of an anchor plate

Methodology Applied
Scientific EffectDeposition: Deposition (physical)

Implementation Method 5

Drying the sample solution with matrix material produces a relatively uniform, thin crystal layer that is ideal for a matrix-assisted ionization (e.g. MALDI)

Methodology Applied
Scientific EffectDrying: Desiccation

Data Source

PatentUS11145499B2Mass spectrometric sample preparation for matrix-assisted ionization
Publication Date: 2021.10.12 BRUKER DALTONIK GMBH & CO KG
  • US11145499B2 patent drawing
  • US11145499B2 patent drawing

AI summary

The invention relates to the preparation of samples for mass spectrometric analyses with matrix-assisted ionization (e.g. MALDI), particularly using the matrix material 2,5-dihydroxyacetophenone (DHAP), and comprises sample preparation in microvessels with the addition of beads or other solid bodies. In this way, particularly thorough mixing can be achieved by shaking (“vortexing”) the microvessels, on the one hand, while crystallization of the matrix material can be initiated in the liquid, on the other hand. It is sufficient to have around 5 to 15 glass beads, 0.5 millimeters in diameter, which scrape against each other and against the vessel wall, and thus cause a DHAP solution to start becoming turbid after one to two minutes by forming tiny crystal nuclei. This allows simultaneous, fully automated preparation of, in particular, a large number of samples, including pipetting onto sample support plates by means of a pipetting and shaking robot.