Mass Spectrometry Laboratory

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MALDI Sample Preparation

The ideal sample preparation in MALDI would be a homogenous layer of small matrix crystals containing a solid solution of the analyte.

To obtain the best result, there is a choice of different matrices as well as preparation techniques. The choices depend on the nature of the analyte.

One aim is to obtain a homogenous preparation of the matrix, both in terms of sample distribution and in term of the sample geometry.

Preparing the sample on the target

Like the choice of the matrix compound, there is also a choice of how to actually prepare the sample. This section discusses the conventional targets. Anchor-targets have to be prepared using specialized anchor-chip protocols (refer to the anchor chip manual).

The chemicals should be of highest available purity.

Saturated matrix solutions should be prepared freshly.

Dried droplet method

A saturated matrix solution is prepared. Unless special solbents have to be used, the solvent used is TA (33% Acetonitrile, 0.1% TFA).

This matrix solution is mixed in equal volumes with the sample solution. The mixture is pipeted on the target (0.5 to 1 µl) and dried at ambient temperature.

The preparation might yield relatively large crystals on the target surface.

The advantages of this method are:

- the method is suitable if the sample contains organic solvents;

- if a "sweet spot" is found on the preparation, a large number of laser shots can be applied to that spot;

- if the sample contains contaminants, there is a chance, that analyte and contaminants will crystallize at spatially different regions on the target;

- the sample can be washed after the crystallization to remove salts;

- the sample can also be recrystallized after washing.

Disadvantages include the need to search for sweet spots and the limited resolution due to the large crystals.