What is Mass Spectrometry Imaging (MSI): Revealing the location of molecules on a tissue section
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Mass spectrometry imaging (MSI) is a technique that visualises the spatial distribution of molecules based on their molecular mass. It involves acquiring mass spectra point by point directly from a sample (such as a tissue section), and then reconstructing a two-dimensional image from the signal intensity at each measurement point, thereby revealing the ‘location’ and ‘relative abundance’ of a particular compound within the tissue.
Basic Principles
The biological sample is first fixed, sectioned and mounted onto a microscope slide; a focused ionisation source (laser, charged droplet or ion beam) is then used to scan the sample surface point by point. At each scanned location, the mass spectrometer records a mass spectrum; once all locations have been scanned, the corresponding signals are extracted based on the mass-to-charge ratio (m/z) of the target compound, and the signal intensity is mapped onto a coordinate system to produce a spatial distribution map of that compound.
Compared with traditional staining or immunohistochemistry, MSI does not require prior labelling with fluorescence or antibodies, nor does it require the specific molecule to be identified to be specified in advance. A single scan can simultaneously yield distribution information for hundreds or even thousands of compounds.
Mainstream ionisation methods
Different ionisation methods determine the desorption mechanism, suitable molecular types and spatial resolution (Source: Wikipedia “Mass spectrometry imaging”):
SIMS (Secondary Ion Mass Spectrometry): A focused ion beam is used to sputter the surface; this offers the highest resolution (<10>
MALDI (Matrix-Assisted Laser Desorption/Ionisation): A laser is directed at the matrix-sample co-crystallisation point; resolution is approximately 20 μm; suitable for larger molecules such as lipids, peptides and proteins.
DESI (Desorption Electrospray Ionisation): A charged solvent mist is sprayed onto the sample surface; resolution is approximately 50 μm; the sample requires virtually no pre-treatment and the technique can operate at atmospheric pressure.
Techniques such as NanoSIMS can achieve quantitative imaging at the subcellular scale.
Value and Applications
MSI has become one of the key technologies in fields such as basic medicine, pharmacology and microbiology, used to localise biomarkers, track the distribution of drugs within the body and study tumour metabolic heterogeneity. Its signal intensity is proportional to the relative abundance of the analyte; once challenges such as sample preparation and matrix effects have been overcome, relative quantification can be performed.
Relation to Neo Source Products
Neo Source INSTRUMENT’s two imaging ion sources, the MSI DPI and MSI LDPI, are based on the DESI+PI and LDI+PI approaches respectively. When fitted to mass spectrometers from Agilent, AB SCIEX or Thermo, they enable mass spectrometry imaging.
References
Wikipedia: Mass spectrometry imaging. https://en.wikipedia.org/wiki/Mass_spectrometry_imaging
McDonnell LA, Heeren RMA. Imaging mass spectrometry. Mass Spectrometry Reviews. 2007;26(4):606–643.
Bodzon-Kulakowska A, Suder P. Imaging mass spectrometry: Instrumentation, applications, and combination with other visualisation techniques. Mass Spectrometry Reviews. 2016;35(1):147–169.