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.

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

Sciex QSTAR XL

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

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

HTX Imaging TM-Sprayer

• Robotic MALDI matrix deposition system

Selected publications

• SpectralAnalysis: Software for the Masses, Alan M. Race, Andrew D. Palmer, Alex Dexter, Rory T. Steven, Iain B. Styles, and Josephine Bunch, Anal. Chem., 88 (19), pp 9451–9458 (2016)
• Probing the Relationship Between Detected Ion Intensity, Laser Fluence, and Beam Profile in Thin Film and Tissue in MALDI MSI, Steven RT, Race AM, Bunch J., J Am Soc Mass Spectrom, 27: 1419–1428 (2016)
• Investigating MALDI MSI parameters (Part 1) - A systematic survey of the effects of repetition rates up to 20kHz in continuous raster mode, Steven RT, Dexter A, Bunch J. Methods, 104: 101–110 (2016)
• Investigating MALDI MSI parameters (Part 2) - On the use of a mechanically shuttered trigger system for improved laser energy stability, Steven RT, Dexter A, Bunch J. Methods, 104: 111–117 (2016)
• Optimisation of colour schemes to accurately display mass spectrometry imaging data based on human colour perception, Race AM, Bunch J. Anal Bioanal Chem., 407: 2047–2054 (2015)

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