What do MALDI MS and MALDI MSI do?

MALDI is a soft ionisation technique used in mass spectrometry allowing the analysis and imaging of a wide range of molecules, including: proteins, peptides, lipids, drugs and metabolites, carbohydrates, nucleic acids, synthetic polymers and large organic compounds. MALDI MSI (imaging) presents a powerful platform for the analysis of a variety of different endogenous and exogenous molecules directly on cells or in tissue sections with femtomolar sensitivity. A great advantage of mass spectrometry is that multiple analytes can be monitored simultaneously, from a single sample section, without prior knowledge of their identities. Also in principle, there is no requirement for the use of target-specific reagents such as chemical tags, antibodies or large dye labels. Therefore, the insights into biological processes are provided with little or no disturbance of the native distributions of molecules in the samples.

How does MALDI MS work?

In MALDI MS a matrix compound, usually a small organic acid, is applied to the sample surface, where co-crystallisation of the sample with the matrix takes place. Ionisation of analytes occurs when the dried matrix is irradiated with a focused laser beam. The energy from the laser is absorbed by the matrix, resulting in a rapid desorption of the molecules from the radiated spot. A mass spectrum of the ions is then recorded. A molecular image may be formed by firing the laser in an ordered array on the sample. 

MALDI MS Image of the drug distribution in a rat lung tissue section, courtesy of Dr Peter Marshall & Josie Morrell, GlaxoSmithKline (GSK). All animal studies were ethically reviewed and carried out in accordance with Animals (Scientific Procedures) Act 1986 and the GSK Policy on the Care, Welfare and Treatment of Animals

What is MALDI MS used for?

• Study of drug metabolite pharmacokinetics.
• Identification of disease biomarkers.
• Detection and quantitation of biomolecules.
• Protein, peptide and amino acid analysis, including intact mass, sequencing and post-translational modifications.
• Identification of microorganisms such as bacteria and fungi.
• Analysis of large organic compounds.
• Characterisation of synthetic polymers.

What are the measurement challenges?

NPL is establishing a new metrology programme to support MALDI MSI. The principal focus of our research is to:

1. Characterise the noise distribution in mass spectrometers for MALDI MSI. This is essential for statistically meaningful use of multivariate analytical techniques which are of increasing importance for data analysis.
2. Improve the fundamental understanding of the analyte-matrix interaction using NPL’s powerful surface chemical analytical techniques, including 3D-SIMS with argon cluster sputtering. 
3. Develop a MALDI MSI source with cellular spatial resolution. This source will be used to study fundamentals of the MALDI MS process.
4. Work with the community, including COST Action BM1104, help support pre-normative interlaboratory studies and the development of standards.
5. Support the uptake of advanced MSI methods into business and academia.