Matrix-assisted laser desorption / ionization

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Scheme of ionization in the MALDI process

Matrix-assisted laser desorption / ionization ( English Matrix-assisted laser desorption / ionization , MALDI ) is a process for the ionization of molecules . Since its development by Franz Hillenkamp and Michael Karas in the 1980s, it has proven to be particularly effective for the mass spectrometry of large molecules and polymers as well as biopolymers (e.g. proteins), but is also used for the detection of lipids and pigments. The laser does not act directly on the large molecules (which would break if directly impacted), but through a matrix in which they are embedded.

The main area of ​​application for MALDI-MS is usually the area of ​​medical research. In addition, the technology is used for biological issues, such as the investigation of polymerization reactions in complex mixtures without sample preparation in quick, chronological order. In recent years also in environmental sciences. The latter is particularly due to the possibility of obtaining high-resolution data on the paleoclimate .

Most of the time, the term MALDI is also used as a short form for MALDI mass spectrometry (MALDI-MS; MALDI-TOF -MS). Due to the high mass accuracy and the applicability to a huge number of different molecules, the MALDI-MS can be used in many areas. The technology used also makes it possible to use MALDI-MS as an imaging method for tissue sections. Different biomarkers can be distinguished in tissue sections.

The process was developed by Franz Hillenkamp and Michael Karas in 1985. Koichi Tanaka received the Nobel Prize in 2002 for a similar process (Soft Laser Desorption, SLD), developed around the same time but not announced until 1987 . Crucially, Tanaka first applied it to proteins.


MALDI is based on the co-crystallization of matrix and analyte with a 100 to 100,000-fold molar excess of matrix molecules. Analyte molecules must be “built into” the crystals of the MALDI matrix while the crystals are forming. Typically, successful cocrystallization requires a matrix-to-analyte ratio of about 5000: 1 (mol / mol). Small organic molecules are selected as matrix substances which strongly absorb energy at the laser wavelength used (e.g. nitrogen laser at a wavelength of 337.1  nm ) (e.g. sinapic acid , 2,5-dihydroxybenzoic acid , α-cyanohydroxycinnamic acid , 2, 4,6-trihydroxyacetophenone ). The excitation takes place with short, high-energy laser pulses with a pulse duration of 2–5  ns , which after relaxation in the crystal lattice leads to explosive particle detachment on the surface of the crystal . Together with the matrix, the enclosed analyte molecules are transferred into the vacuum of the mass spectrometer and are thus accessible for mass spectrometric analysis.

Sample preparation and application to the sample plate are essential for a MALDI measurement . There are various options for this, such as the Dried Droplet method (= mixing the analyte and matrix solution, with subsequent evaporation of the solvents used) or thin-layer preparation .

The ionization mechanism at MALDI is not yet fully understood. There are currently two preferred options:

  1. The starting point for the measurement is the analyte in its pH- determined form in the matrix (probably in a solvent pocket in the crystal). A laser pulse detaches clusters from the surface. The clusters contain the analyte as well as corresponding counterions and an excess of matrix. As the process progresses, the matrix evaporates and the analyte is desolvated . Corresponding counter ions are neutralized and also evaporate. Then there is a multiply charged analyte ion, which loses further charges by capturing electrons and is then only detected as having a single charge. This theory of charge separation cannot yet be proven.
  2. A photoionization would lead to the same results, which is also available in the literature discussion whether the power would be enough for it.

See also

Web links

Individual evidence

  1. Michael. Karas, Franz. Hillenkamp: Laser desorption ionization of proteins with molecular masses exceeding 10,000 daltons . In: Analytical Chemistry . tape 60 , no. 20 , October 15, 1988, ISSN  0003-2700 , pp. 2299-2301 , doi : 10.1021 / ac00171a028 .
  2. Pierre Chaurand, Markus Stoeckli, Richard M. Caprioli: Direct Profiling of Proteins in Biological Tissue Sections by MALDI Mass Spectrometry . In: Analytical Chemistry . tape 71 , no. December 23 , 1999, ISSN  0003-2700 , pp. 5263-5270 , doi : 10.1021 / ac990781q .
  3. Mark Stoeckli, Pierre Chaurand, Dennis E. Hallahan, Richard M. Caprioli: Nature Medicine . tape 7 , no. 4 , p. 493-496 , doi : 10.1038 / 86573 .
  4. ^ Astrid Vieler, Christian Wilhelm, Reimund Goss, Rosmarie Süß, Jürgen Schiller: The lipid composition of the unicellular green alga Chlamydomonas reinhardtii and the diatom Cyclotella meneghiniana investigated by MALDI-TOF MS and TLC . In: Chemistry and Physics of Lipids . tape 150 , no. 2 , December 2007, p. 143-155 , doi : 10.1016 / j.chemphyslip.2007.06.224 .
  5. Ch. Krösche, MG Peter: Detection of Melanochromes by MALDI-TOF Mass Spectrometry . In: Tetrahedron . tape 52 , no. 11 , 1996, pp. 3947-3952 .
  6. Lars Wörmer, Marcus Elvert, Jens Fuchser, Julius Sebastian Lipp, Pier Luigi Buttigieg: Ultra-high-resolution paleoenvironmental records via direct laser-based analysis of lipid biomarkers in sediment core samples . In: Proceedings of the National Academy of Sciences . tape 111 , no. 44 , November 4, 2014, p. 15669–15674 , doi : 10.1073 / pnas.1405237111 , PMID 25331871 , PMC 4226096 (free full text).
  7. Maldi MS: A Practical Guide to Instrumentation, Methods and Applications . John Wiley & Sons, 2007, ISBN 978-3-527-61047-1 ( ).