MALDI Mass Spectrometry in Biomedicine

Matrix-assisted laser desorption ionization (MALDI) mass spectrometry enables rapid profiling of various biomolecules from both tissues and biofluids.

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Although MALDI was originally used for the analysis of peptides and proteins, it now plays an important role in biomarker discovery, genotyping, identification of microorganisms, lipidomic analysis, and metabolomics.

Improvements in the selection of matrices, matrix crystallization heterogeneity and the use of tools for post-acquisition data exploration, and MALDI mass spectrometry has been applied to study the presence and (in imaging approaches) the distribution of a plethora of biological moieties. This increase in application scope positioned MALDI mass spectrometry as a vital tool in medical research and clinical practice.

MALDI imaging and protein profiling

Protein profiling in biofluids has been successfully employed in a myriad of biomedical areas, such as cancer biomarker research, where it can discriminate between the affected patients and control individuals, and patients before and after operation.

In addition, using MALDI for profiling proteins in urine may identify patients at risk of developing liver injury after treatment with chemotherapeutics, like methotrexate. Similar protocols are also being applied in diabetes and related disorders.

While most analyses in biomedicine that use MALDI protein profiling have analyzed biofluids after extensive samples preparation, some researchers studied biological tissues by using MALDI imaging mass spectrometry for thorough spatial analysis of peptide and protein signals. The objective analysis of profiles may allow the identification of novel disease biomarkers.

Single-nucleotide polymorphism analysis

MALDI mass spectrometry is used to obtain adequate mass accuracy signals for biomolecules of large molecular weight. This involves analysis of short sequence nucleotides and single-nucleotide polymorphisms.

Single-nucleotide polymorphisms are genetic sequence variations of specific genes that may result in phenotypical variations and subsequent susceptibility of humans to specific diseases and their response to certain treatments. They can be convenient indicators of disease risk and to tailor appropriate therapy regimes.

When using MALDI mass spectrometry, various genes and different single-nucleotide polymorphisms can be simultaneously analyzed in case the mass of the primer sequences (together with their extension products) is different enough to be determined independently by the MALDI mass spectrometry profiling process.

MALDI in metabolomics

MALDI mass spectrometry is not frequently used in metabolomic analysis as matrix ions are found in the low mass range (i.e. less than 500 daltons), complicating the resulting spectra. Nonetheless, recently the approach has been used to study metabolism in cancer cells and metabolites from the natural secretions of larvae used in maggot debridement therapy.

The most common utilization of MALDI profiling is in lipidomics where phospholipids are studied in a high-throughput way by using the mass accuracy provided by the time-of-flight tube. This enables the phospholipid grouping and length estimation of fatty acid chains.

Written by

Dr. Tomislav Meštrović

Dr. Tomislav Meštrović is a medical doctor (MD) with a Ph.D. in biomedical and health sciences, specialist in the field of clinical microbiology, and an Assistant Professor at Croatia's youngest university – University North. In addition to his interest in clinical, research and lecturing activities, his immense passion for medical writing and scientific communication goes back to his student days. He enjoys contributing back to the community. In his spare time, Tomislav is a movie buff and an avid traveler.