National Physical Laboratory

Matrix assisted laser desorption / ionization (MALDI) mass spectrometry

MALDI mass spectrometry 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 to a wide range of analytes, including: lipids; drugs and metabolites; proteins; peptides; carbohydrates; polymers; and large organic compounds.

In MALDI MS, a matrix compound is applied to the sample surface, typically by a robotic sprayer or a sublimation technique. Analyte ionisation occurs when the matrix is irradiated by 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 produced may then be recorded. A molecular image may be formed by firing the laser in an ordered array on the sample, or continuously rastering the beam across the sample surface, with typical pixel sizes of 1-50 µm.

NPL is leading the understanding fundamental aspects of MALDI and the associated metrology challenges, including laser variables, matrix chemistry and deposition technique. NiCE-MSI is also focusing on improving throughput, sensitivity and lateral resolution, as well as methods of quantification and normalisation.

These fundamental studies complement application of MALDI MSI to answer biological questions from collaborators and stakeholders from academia and industry, including the localisation and quantification of drugs and metabolites, and the identification of disease biomarkers.

MALDI-MSI images of rat kidney (45 µm pixel size, unpublished data). Non-negative matrix factorisation (NMF), performed after isolation of tissue region by principal components analysis (PCA), isolates the renal medulla (green, factor 2), renal cortex (ma
MALDI-MSI images of rat kidney (45 µm pixel size, unpublished data). Non-negative matrix factorisation (NMF), performed after isolation of tissue region by principal components analysis (PCA), isolates the renal medulla (green, factor 2), renal cortex (magenta, factor 3), renal pelvis (blue, factor 4) and vasculature (red, factor 10).


The size and complexity of mass spectrometry imaging data presents a challenge to data analysis. NiCE-MSI is developing tools to convert, process and visualise MSI data sets from multiple instruments and techniques using memory efficiency process. With potentially thousands of m/z peaks per pixel, identifying ion images that reflect the pathology or anatomy in the sample is challenging. Multivariate techniques such as principal components analysis or non-negative matrix factorisation, and segmentation algorithms such as k-means, enable effective and efficient identification of ions of interest and their distribution. NiCE-MSI continues apply and develop these and associated techniques.

Instrumentation

Waters Synapt G2-Si MALDI

  • Q-TOF mass spectrometer with ion mobility
  • Variable repetition rate Nd:YAG laser
  • Travelling wave ion mobility provides separation by collisional cross-sectional area, as well as mass-to-charge ratio
Waters Synapt G2-Si MALDI
Waters Synapt G2-Si MALDI


Sciex QSTAR XL

  • Qq-ToF mass spectrometer
  • Sciex oMALDI II ion source with raster-mode imaging
Sciex QStar XL with oMALDI II source
Sciex QStar XL with oMALDI II source


Thermo LTQ Orbitrap Velos

  • High-resolution orbitrap mass spectrometer
  • Custom atmospheric, transmission mode MALDI source
  • MassTech AP-MALDI source
  • ESI source
  • DESI and LESA ambient MS sources
  • Laser bench for fundamental studies including Elforlight Nd:YAG and Nd:YVO4 lasers
  • Fibre beam delivery to Sciex oMALDI II source on QSTAR XL or custom AP-TM-MALDI source on Orbitrap Velos
Laser bench and Thermo LTQ Orbitrap Velos with custom AP-TM-MALDI source
Laser bench and Thermo LTQ Orbitrap Velos with custom AP-TM-MALDI source


HTX Imaging TM-Sprayer

  • Robotic MALDI matrix deposition system

Selected publications

Measurement services

If you are interested in accessing the techniques and expertise available at NiCE-MSI and NPL, there are many ways of working with us.

Contact

Josephine Bunch

Last Updated: 30 Oct 2017
Created: 16 Nov 2016

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