Mass spectrometer with maldi laser system

Abstract

The invention relates to a mass spectrometer comprising a laser system for mass-spectrometric analyses with ionization of analyte molecules in a sample by matrix-assisted laser desorption. A mass spectrometer with a pulsed UV laser system produces a spatially distributed spot pattern with peaks of uniform energy density on the sample, increasing thereby the degree of ionization for analyte ions as compared to conventional spot patterns. The spot pattern with peaks of uniform energy density can be produced by homogeneous illumination of a pattern generator, for example a lens array. The homogeneous illumination can be generated by a low-cost beam-shaping element, which does not act on the UV beam but on the original infrared beam, in conjunction with changes to the beam cross-section and beam profile brought about by the nonlinear conversion crystals. This beam shaping not only produces a beam profile which illuminates the pattern generator homogeneously with low losses, but at the same time increases the efficiency of the frequency multiplication and the lifetime of the conversion crystals so that cost savings are achieved because less laser energy is required and the lifetime is increased.

Description

PRIORITY INFORMATION[0001]This patent application claims priority from German Patent Application No. 10 2011 116 405.0 filed on Oct. 19, 2011, which is hereby incorporated by reference in its entirety.FIELD OF THE INVENTION[0002]The invention relates to a mass spectrometer comprising a laser system for mass-spectrometric analyses with ionization of analyte molecules in a sample by matrix-assisted laser desorption.BACKGROUND OF THE INVENTION[0003]During the past twenty years, two methods have become established in the mass spectrometry of biological macromolecules: ionization by matrix-assisted laser desorption (MALDI), and electrospray ionization (ESI). The biological macromolecules to be analyzed are termed analyte molecules below. In the MALDI method, the analyte molecules are generally prepared on the surface of a sample support in a solid, polycrystalline matrix layer, and are predominantly ionized with a single charge, whereas in the ESI method they are dissolved in a liquid an...

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Benefits of technology

[0016]An infrared solid-state laser system may be used. Economic advantages can be realized, for example, by the fact that, firstly, beam-shaping elements for infrared light cost significantly less than beam-shaping elements for ultraviolet light; secondly, the nonlinear conversion crystals can be utilized better and with a higher conversion rate due to the rectangular cross-section and the homogeneous energy density; thirdly, the lifetime of the conversion crystals increases; and fourthly, the beam has a cross-section at the exit of the conversion crystals which has a homogeneous energy density in a square middle section containing more than 90 percent of the beam energy. It is thus ideal for homogeneous illumination of the pattern generator without substantial parts of this higher-energy light having to be cut off and destroyed.

[0017]Thus, a mass spectrometer with a pulsed UV laser system is proposed, with relatively low energy consumption, which produces a spatially distributed spot pattern with peaks of uniform energy density on the sample, increasing the degree of ionization for analyte ions as compared to conventional spot patterns. The spot pattern with peaks of uniform energy density can be produced by homogeneous illumination of a pattern generator, for example a lens array. The homogeneous illumination can be generated by a low-cost beam-shaping element, which does not act on the UV beam but on the original infrared beam, in conjunction with changes to the beam cross-section and beam profile brought about by the nonlinear conversion crystals. This beam shaping not only produces a beam profile that illuminates the pattern generator homogeneously with low losses, but at the same time increases the efficiency of the frequency multiplication and the lifetime of the conversion crystals so that significant cost savings are achieved because less laser energy is required and the lifetime is increased.

Problems solved by technology

A further increase in the energy density by a factor of 3 would be able to increase the degree of ionization for analyte molecules to more than 10 percent, but would hopelessly oversaturate the ion detector system.

Furthermore, increasing the energy density causes a simultaneous increase in the number of “metastable” ions; these are ions that decay on their way to the ion detector and cannot reach the ion detector for ion-optical reasons.

If the number of metastable ions becomes too high, the degree of ionization can still increase, but the number of detectable ions cannot.

The MALDI process is complex, and is affected by numerous factors, some of which are interdependent.

This preparation distributes analyte molecules extremely inhomogeneously in the matrix crystal complexes, however, and can scarcely be used for quantitative analyses.

The ion yield from a Gaussian profile spot with a diameter of around 100 micrometers was extremely low and had to be compensated for by increasing the energy density; but this caused a deterioration in the mass resolution and an enormous increase in sample consumption, partly because liquefied matrix material was splashed away during the desorption process.

Furthermore, the adjustment of the laser beam transverse to the pattern generator is very demanding.

In order to achieve laser pulse rates of 10 kilohertz, it is advisable to be careful with the laser energy and not destroy most of the UV light produced, because otherwise the high power demands would make the laser systems far too expensive and complex.

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