Rapidly becoming a complementary technology in the field of biology due to the global development of mass spectrometry, Matrix-Assisted Laser Desorption/Ionisation (MALDI) is a soft ionisation technique developed in 1987 by Koichi Tanaka of Shimadzu Corporation and his colleagues who received the 2002 Nobel Prize in Chemistry. While the first reported use of MALDI for imaging was in 1984, it was brought to light by the Caprioli group at the University of Texas Medical School in 1997. Since 2010, this instrument has continued to attract the interest of researchers in the (bio-)medical but also forensic fields and is now the most widely used mass spectrometry imaging technique in R&D. In this article, Alcimed presents 3 innovative application areas of this booming technology.
Like most mass spectrometry imaging techniques, MALDI offers the possibility of acquiring both an image of the sample being analysed and a mass spectrum per pixel of that same image. This forms a 3-dimensional data cube, allowing the spatial distribution of biomolecules to be visualised.
One of the advantages of this technique is the analysis of large molecules (i.e. proteins, RNA, DNA, polymers and other macromolecules) that are difficult to analyse using more conventional methods, as well as the visualisation of their spatial distribution. In addition to the image/mass spectra duality, this technology offers the possibility of discovering and characterising different chemical species in intact tissues, with low sample alteration during analysis, good precision, high sensitivity and a speed of analysis that can range from a few minutes to a few hours depending on the parameters selected.
In the field of medicine, MALDI-MSI is now positioned as a promising complementary technique, in order to offer a more precise diagnosis and/or to better understand the mechanisms of evolution of certain pathologies.
For example, in renal cancers, the differentiation of tumour subcategories remains a major challenge due to their histological similarities within the tissues. Their classification currently requires a high level of expertise and relies mainly on visual deductions. With this in mind, MALDI-MSI provides detailed histological-molecular profiles. In combination with a data classification algorithm, this technology has been shown to correctly diagnose 87% of patients in a recent study [1,2].
In another context, the molecular mechanisms of some diseases remain relatively unclear, making their diagnosis difficult.
Neurologic diseases or injuries such as Alzheimer’s, Parkinson’s or epilepsy are major public health concerns. In neurology, the ability to visualise the spatial distribution of molecules – without the need for labelling – using MALDI mass spectrometry imaging is an asset. Its use in neurology offers the possibility to quickly and easily identify target areas of the brain in order to guide researchers in the development of new therapies as well as to better understand the mechanisms of injuries or pathologies.
The diagnosis of these diseases is also an important element in the forensic world in order to determine cause of death and provide answers to families. This is particularly the case for cardiac ischaemia, a disease that is the cause of many deaths, for which a post-mortem diagnosis can only be made if the ischaemia persists for at least 6 to 12 hours, after which time morphological alterations appear in the myocardium. The use of MALDI mass spectrometry imaging technology has revealed important metabolic changes during the first hours of the disease, offering the opportunity of identifying metabolic markers for early post-mortem diagnosis of the disease as well as a better understanding of the internal mechanisms of this pathology.
Advances in instrumentation and analytical methods have led to the increasing acceptance and use of MALDI-MSI in the pharmaceutical research community. With more and more research in the field, this technology is now becoming a key solution in the improvement and/or development of new treatments.
When designing new drugs, understanding their bio-distribution, metabolism and accumulation in the body are key factors. With this in mind, MALDI-MSI is now a tool for visualising the penetration of certain drug compounds and their metabolites into tissues such as the skin.
Beyond the visualisation of drug distribution in tissues, MALDI-MSI can now also provide evidence of the action of a compound on a tissue, for example by highlighting pharmacodynamic markers or detecting metabolic changes.
This technology can also provide useful information on the adverse effects of drugs such as off-target activity and toxicology. It has already been successfully applied to several drug compounds used in dermatology (i.e. mycoses) or in the treatment of liver and kidney tumours.
MALDI-MSI technology can be applied to any type of biological sample, such as fingerprints, a widely used in forensics. Made up of sweat and deposits from the rest of the glands on the human body, these traces are a source of information that is not yet exploited to its full potential. In addition to the pattern on our fingertips that can be seen in CSI or the DNA it contains, the chemical composition of fingerprints is a gold mine of information that can be used to learn more about a person’s habits, what they have been in contact with or their state of health through MALDI-MSI analysis.
The set of molecules that make up these traces is, a particular combination that makes it possible, to differentiate between individuals. In the spirit of minimising the risk of altering the evidence, the application of MALDI mass spectrometry imaging to this type of biological sample makes it possible to obtain both an image of the papillary residue and its chemical composition, while keeping the fingermark visually intact.
Its recent real-life application has narrowed the circle of suspects by detecting a cannabis metabolite characteristic of a certain type of consumption.
The detection of many types of compounds thanks to MALDI-MSI technology in relation to our habits or the consumption of medicines or drugs in fingerprints also opens many doors to the biomedical field for the implementation of less invasive analysis methods for the detection of certain pathologies.
A promising, non-destructive technology, MALDI mass spectrometry imaging is gradually gaining ground in the pharmaceutical and biomedical fields with the improvement of diagnoses and the development of new treatments; but also in the particular field of forensics with a new way of exploiting collected evidence.
Easy to use, the main limitation at present is the cost of the instrument itself. However, with more and more research being published each year, it is hoped that this will decrease through the establishment of collaborations, for example. Currently reserved for large universities or specialised research centres, it is very likely that MALDI mass spectrometry imaging will spread widely within the health industry over the next few years.
If your organisation is active in mass spectrometry imaging, exploring innovations in MALDI mass spectrometry imaging or working to improve disease diagnostics, please contact us, our Health team can support you!
Sources :
[1] Advances in MALDI Mass Spectrometry Imaging Single Cell and Tissues, Zhu et al., 2022
[2] Histo-molecular differentiation of renal cancer subtypes by mass spectrometry imaging and rapid proteome profiling of formalinfixed paraffin-embedded tumor tissue sections, Moginger et al., 2020
About the authors,
Marie, Consultant and Quentin, Project Manager, in Alcimed’s Life Sciences team in Swizterland
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