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Innovative Molecular Imaging Using Spatially Controlled Ionization Combined with High Performance FT-ICR Mass Spectrometry


EMSL Project ID
40892

Abstract

The objective of this proposed 3 year EMSL-FOM institute AMOLF partnership is to incorporate C60 SIMS and MALDI ionization techniques with a 9.4 Tesla FT-ICR mass spectrometer to enable and enhance the spatial analysis of proteins, peptides, lipids, metabolites and other bio-molecules found in complex biological systems. The MALDI ionization technique combined with precision translational control of a tissue sample surface has allowed for the molecular imaging of biomolecules with a spatial resolution of 10 micrometers. C60 ion sources have achieved sub-micron spatial resolution. Combining these ionization methods with high resolution Fourier-transform ion cyclotron (FT-ICR) mass spectrometry (MS) will enhance the detailed local characterization of the biomolecular composition on complex surfaces such as cells, tissues and microbial biofilms. The high resolution, mass measurement accuracy, and advanced tandem MS capabilities of FT-ICR MS will greatly aid in the accurate identification of biomolecules. Ion funnel technology will be incorporated in the source of the 9.4T FT-ICR mass spectrometer to enable enhanced capture of biomolecules ionized by the MALDI and C60 methods and provide a dramatic improvement in attainable sensitivity and throughput of bio-surface analysis beyond the state-of-the-art. Developing and deploying this new instrumentation platform has potential as a transformational tool for the biological and environmental sciences via EMSL. The spatial characterization of biomolecules has developed from the initial demonstration phase into providing biologically relevant information and the Heeren group at the FOM -AMOLF has played a leading role in this development. Through this partner proposal EMSL would leverage previous FOM-AMOLF efforts to develop mass spectrometry based bioimaging techniques with the high performance capabilities located at EMSL. Through this collaboration, EMSL would gain a unique opportunity to leverage existing technologies in mass spectrometry and biomolecule analysis with the leading bioimaging methods and technologies developed at FOM-AMOLF. Extension of these efforts will also be incorporated into the High Resolution and Mass Accuracy Capability (21T FT-ICR MS being the most likely alternative) that is currently being planned.

Project Details

Project type
Scientific Partner
Start Date
2010-09-01
End Date
2013-09-30
Status
Closed

Team

Principal Investigator

Ronald Heeren
Institution
Maastricht University

Team Members

Christopher Anderton
Institution
Environmental Molecular Sciences Laboratory

Errol Robinson
Institution
Pacific Northwest National Laboratory

David Brown
Institution
Environmental Molecular Sciences Laboratory

Ljiljana Pasa-Tolic
Institution
Environmental Molecular Sciences Laboratory

David Koppenaal
Institution
Environmental Molecular Sciences Laboratory

Related Publications

Leach FE, III, RV Norheim, GA Anderson, and L Pasa-Tolic. 2014. "Application of Printed Circuit Board Technology to FT-ICR MS Analyzer Cell Construction and Prototyping." Journal of the American Society for Mass Spectrometry 25(12):2069-2072. doi:10.1007/s13361-014-0952-6
Lu J, K Chughtai, SO Purvine, ZM Bhujwalla, V Raman, L Pasa-Tolic, RM Heeren, and K Glunde. 2015. "MALDI-mass spectrometric imaging reveals hypoxia-driven lipids and proteins in a breast tumor model." Analytical Chemistry. doi:10.1021/ac504503x
Roempp, A.; Both, J.; Brunelle, A.; Heeren, R. M. A.; Laprévote, O.; Prideaux, B.; Seyer, A.; Spengler, B.; Stoeckli, M.; Smith, D. F. Mass Spectrometry Imaging of Biological Tissue: An Approach for Multicenter Studies. Anal. Bioanal. Chem., Vol. 407, No. 8, pp. 2329-2335, 2015. DOI 10.1007/s00216-014-8410-7
Smith DF, A Kharchenko, M Konijnenburg, I Klinkert, L Pasa-Tolic, and RM Heeren. 2012. "Advanced Mass Calibration and Visualization for FT-ICR Mass Spectrometry Imaging." Journal of the American Society for Mass Spectrometry 23(11):1865-1872. doi:10.1007/s13361-012-0464-1.
Smith DF, A Kiss, FE Leach, III, EW Robinson, L Pasa-Tolic, and RM Heeren. 2013. "High Mass Accuracy and High Mass Resolving Power FT-ICR Secondary Ion Mass Spectrometry for Biological Tissue Imaging." Analytical and Bioanalytical Chemistry 405(18):6069-6076. doi:10.1007/s00216-013-7048-1.
Smith DF, DP Kilgour, M Konijnenburg, PB O'Connor, and RM Heeren. 2013. "Absorption Mode FT-ICR Mass Spectrometry Imaging." Analytical Chemistry 85(23):11180-11184. doi:10.1021/ac403039t
Smith DF, EW Robinson, AV Tolmachev, RM Heeren, and L Pasa-Tolic. 2011. "C60 Secondary Ion Fourier Transform Ion Cyclotron Resonance Mass Spectrometry." Analytical Chemistry 83(24):9552-9556. doi:10.1021/ac2023348.
Smith, D. F.; Konijnenburg, M.; Schulz, C.; Kilic, M.; Heeren, R. M. A. Distributed Computing Strategies for Processing of FT-ICR MS Imaging Datasets for Continuous Mode Data Visualization. Anal. Bioanal. Chem., Vol. 407, No. 8, pp. 2321-2327, 2015.