MALDI Technique

What is MALDI and how does it work?

Matrix-Assisted Laser Deposition/Ionization (MALDI) is a sample preparation technique used to prepare an analyte for mass spectrometry. MALDI is a relatively gentle technique, which usually allows molecules to be analyzed without significant fragmentation.

The process begins by mixing the analyte with a matrix – usually a crystalline material dissolved in a solvent. The analyte/matrix solution is then spotted onto a metal plate, ready to begin the ionization process.

Next, the solution is irradiated with pulsed laser light. This causes the solution to desorb from the surface of the plate, removing both the matrix and the analyte. Here, the matrix helps to protect the analyte and prevents damage from the intense laser. During this process, a proton is transferred from a matrix molecule to the analyte. This essentially ionizes the analyte, without a need for more intensive methods that could damage the molecule.

Once the analyte is ionized, it can be passed on to a mass spectrometer for analysis. Most often, MALDI is coupled with a Time of Flight - Mass Spectrometer (ToF-MS), which causes the ions to become separated based on their individual masses and charges as they travel the length of the machine. Once the ions reach the end of the spectrometer, they are detected, and data on the masses and concentrations of the components within the sample can be collected.

Why is MALDI used?

MALDI is referred to as a “soft” ionization technique, which means that it can ionize molecules without causing them to break down into fragments. Often, ionization techniques involve removing electrons from the analyte, which in some cases can be too destructive.

In MALDI, ionization occurs through a proton transfer, which is far less destructive to delicate molecules. Furthermore, during the desorption process, the matrix helps to absorb the energy from the laser and protects the analyte from being over-exposed and breaking down. Overall this results in a technique that allows molecules to be analyzed without damaging them first, which in certain fields can be essential.

What are the limitations of MALDI?

Due to the need for an excess matrix, the analyte can sometimes be slightly obscured during analysis. This means that in some cases, small quantities of sample matter require extra optimization steps to achieve high-quality results. Furthermore, particularly large biomolecules can be difficult to identify if existing mass spectrum data does not exist to use as a comparison. Hence, it is always worth considering the type of sample to determine whether MALDI is the most appropriate option.

Sample requirements and preparation

Before MALDI can take place, the sample must first be dissolved in a suitable matrix solution. These can be based on water, organic solvents, or a combination of both, which allows both polar and nonpolar molecules to dissolve. Ideally, the sample should be as pure as possible. Both organic and inorganic contaminants can affect the quality of the results, so contamination should be avoided as far as possible.

Need a mass spectrometry analysis with MALDI preparation?

Measurlabs offers high-quality MALDI-TOF MS analyses for studying large molecules. Please ask for details and request a quote through the form below or by emailing us at info@measurlabs.com. Other mass spectrometry analyses from HRMS to LC-MS are also available.