Dr John S. Fletcher

John Fletcher

Visiting Research Fellow

Department of Chemistry and Molecular Biology
Gothenburg University
412 96 Göteborg
Sweden
tel: ++46 (0)317869105

john.fletcher @ chem.gu.se

  • PhD on ToF-SIMS and Infrared Studies of Sulfuric Acid Hydrates, UMIST
  • MChem in Chemistry, UMIST
John Fletcher

My research is focused on the development of methodologies and instrumentation for imaging mass spectrometry. Particularly I have been focused on the development of secondary ion mass spectrometry (SIMS) for 2 and 3D imaging of biological cells and tissue. SIMS uses an energetic ion beam to bombard a sample leading to the ejection (sputtering) of atomic, fragment and molecular species of which a small portion are ionised and can therefore be extracted and analysed by mass spectrometry. The probing ion beams can be focused to sub-micron spot sizes and by scanning the beam over the sample chemical maps can be generated like a chemical microscope.

The introduction cluster and polyatomic ion beams has improved the ability of molecular species to be imaged by SIMS. Polyatomic ion beams particularly C60 have provided the ability to not only image the sample surface but to generate 3D molecular images. The polyatomic ions deposit most of their energy in the uppermost surface layers of the sample and hence continued analysis no longer results in the rapid accumulation of sub-surface chemical damage that results in a loss of molecular signal from the sample.

To fully exploit the properties of these new beams instrumentation has been developed that allows the mass spectrometry to be de-coupled from the sputtering process. The J105 –3D Chemical Imager has been developed in collaboration with Ionoptika Ltd and provides a 103 increase in duty cycle while maintaining mass resolution with high resolution imaging.

J105Ionoptika J105 — 3D Chemical Imager
(click for animation)

Current research themes

Biological imaging

A number of tissue and cell imaging projects are currently under way. Sample preparation for analysis under the vacuum conditions required for SIMS is critical to generating useful data and optimisation of this aspect of the experiment is a continuing challenge.

Accurate data interpretation and visualisation is also crucial if biological questions are to be answered, particularly the SIMS data can be quite complex (and computationally taxing). Methods are being developed for 3D data reconstruction/visualisation along with ways of efficiently extracting important information from the large data sets.

Instrumentation

  • Characterising the interaction of new ion beams with surfaces, particularly for the application to 3D molecular imaging.
  • Investigating new gas cluster ion beams (GCIB) such as Arn that may provide ‘softer’ ejection of material from the sample and therefore reduce fragmentation of molecular species and improve depth resolution.

Publications

49 Peptide Fragmentation and Surface Structural Analysis by Means of ToF-SIMS Using Large Cluster Ion Sources
Yuta Yokoyama, Satoka Aoyagi, Makiko Fujii, Jiro Matsuo, John S. Fletcher, Nicholas P. Lockyer, John C. Vickerman, Melissa K. Passarelli, Rasmus Havelund and Martin P. Seah
Analytical Chemistry 88 (2016) 3592–3597
48 Evaluation of biomolecular distributions in rat brain tissues by means of ToF-SIMS using a continuous beam of Ar clusters
Shusuke Nakano, Yuta Yokoyama, Satoka Aoyagi, Naoyuki Himi, John S. Fletcher, Nicholas P. Lockyer, Alex Henderson and John C. Vickerman
Biointerphases 11 (2016) 02A307
47 Prospect of increasing secondary ion yields in ToF-SIMS using water cluster primary ion beams
S. Sheraz (née Rabbani), A. Barber, I. Berrueta Razo, J. S. Fletcher, N.P. Lockyer and J. C. Vickerman
Surf. Interface Anal. 46 (2014) 51–53
46 Spatiotemporal lipid profiling during early embryo development of Xenopus laevis using dynamic Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) Imaging
Hua Tian, John S. Fletcher, Raphael Thuret, Alex Henderson, Nancy Papalopulu, John C. Vickerman and Nicholas P. Lockyer
Journal of Lipid Research 55 (2014) 1970-1980
45 Peptide structural analysis using continuous Ar cluster and C60 ion beams
Satoka Aoyagi, John S. Fletcher, Sadia Sheraz (Rabbani), Tomoko Kawashima, Irma Berrueta Razo, Alex Henderson, Nicholas P. Lockyer, John C. Vickerman
Analytical and Bioanalytical Chemistry 405 (2013) 6621-6628
44 Enhancing Secondary Ion Yields in Time of Flight-Secondary Ion Mass Spectrometry Using Water Cluster Primary Beams
Sadia Sheraz née Rabbani, Andrew Barber, John S. Fletcher, Nicholas P. Lockyer, and John C. Vickerman
Analytical Chemistry 85 (2013) 5654–5658
43 Evaluating the challenges associated with time-of-flight secondary ion mass spectrometry for metabolomics using pure and mixed metabolites
John S. Fletcher, Helen L. Kotze, Emily G. Armitage, Nicholas P. Lockyer, John C. Vickerman
Metabolomics 9 (2013) 535-544
42 Secondary Ion Mass Spectrometry: Characterising complex samples in two and three dimensions.
John Stephen Fletcher and John C. Vickerman
Analytical Chemistry 85 (2013) 610–639
41 The inherent problem of transflection-mode infrared spectroscopic microscopy and the ramifications for biomedical single point and imaging applications
Paul Bassan, Joe Lee, Ashwin Sachdeva, Juliana Pissardini, Konrad M. Dorling, John S. Fletcher, Alex Henderson and Peter Gardner
Analyst 138 (2013) 144-157
40 ToF-SIMS as a tool for metabolic profiling small biomolecules in cancer systems
Helen L. Kotze, Emily G. Armitage, John S. Fletcher, Alex Henderson, Kaye J. Williams, Nicholas P. Lockyer and John C. Vickerman
Surf. Interface Anal. 45 (2013) 277-281
39 Peak picking as a pre-processing technique for imaging time of flight secondary ion mass spectrometry
Jimmy D. Moore, Alex Henderson, John S. Fletcher, Nicholas P. Lockyer and John C. Vickerman
Surf. Interface Anal. 45 (2013) 461-465
38 Time-of-flight SIMS as a novel approach to unlocking the hypoxic properties of cancer
Emily G Armitage, Helen L Kotze, John S Fletcher, Alex Henderson, Kaye J Williams, Nicholas P Lockyer and John C Vickerman
Surf. Interface Anal. 45 (2013) 282-285
37 Comparison of C60 and GCIB primary ion beams for the analysis of cancer cells and tumour sections
John S. Fletcher, Sadia Rabbani, Andrew M. Barber, Nicholas P. Lockyer, John C. Vickerman
Surf. Interface Anal. 45 (2013) 273-276
36 Label free biochemical 2D and 3D imaging using secondary ion mass spectrometry
John S. Fletcher, John C. Vickerman and Nicholas Winograd
Current Opinion in Chemical Biology 15 (2011) 733–740
35 TOF-SIMS with Argon Gas Cluster Ion Beams: A Comparison with C60+.
Sadia Rabbani, Andrew M. Barber, John S. Fletcher, Nicholas P. Lockyer, John C. Vickerman
Analytical Chemistry 83 (2011) 3793–3800
34 Molecular SIMS imaging; spatial resolution and molecular sensitivity: have we reached the end of the road? Is there light at the end of the tunnel?
John S. Fletcher, Nicholas P. Lockyer and John C. Vickerman
Surf. Interface Anal. 43 (2011) 253-256
33 Investigating the effect of temperature on depth profiles of biological material using ToF-SIMS.
Alan Piwowar, John Fletcher, Nicholas Lockyer and John Vickerman
Surf. Interface Anal. 43 (2011) 207-210
32 Top-down approach to studying biological components using ToF-SIMS.
Alan Piwowar, John Fletcher, Nicholas Lockyer and John Vickerman
Surf. Interface Anal. 43 (2011) 265-268
31 Exploring subcellular imaging on the buncher-ToF J105 3D chemical imager.
S. Rabbani, J. S. Fletcher, N. P. Lockyer and J. C. Vickerman
Surf. Interface Anal. 43 (2011) 380-384
30 A new time-of-flight SIMS instrument for 3D imaging and analysis.
Rowland Hill, Paul Blenkinsopp, Stephen Thompson, John Vickerman and John S. Fletcher
Surf. Interface Anal. 43 (2011) 506-509
29 Developments in molecular SIMS depth profiling and 3D imaging of biological systems using polyatomic primary ions.
John S. Fletcher, Nicholas P. Lockyer, John C. Vickerman
Mass Spectrom. Rev. 30 (2011) 142-174
28 Three-dimensional mass spectral imaging of HeLa-M cells - sample preparation, data interpretation and visualisation.
John S. Fletcher, Sadia Rabbani, Alex Henderson, Nicholas P. Lockyer, John C. Vickerman
Rapid Commun. Mass Spectrom. 25 (2011) 925-932
27 Effects of Cryogenic Sample Analysis on Molecular Depth Profiles with TOF-Secondary Ion Mass Spectrometry.
Alan M. Piwowar, John S. Fletcher, Jeanette Kordys, Nicholas P. Lockyer, Nicholas Winograd, and John C. Vickerman
Analytical Chemistry 82 (2010) 8291-8299
26 Time of Flight Mass Spectrometry Imaging of Samples Fractured In Situ with a Spring-Loaded Trap System.
Lanekoff, Ingela; Kurczy, Michael E.; Hill, Rowland; Fletcher, John S.; Vickerman, John C.; Winograd, Nick; Sjoevall, Peter; Ewing, Andrew G.
Analytical Chemistry 82 (2010) 6652-6659
25 A Comparative Study of Secondary Ion Emission from Water Ice under Ion Bombardment by Au+, Au3+, and C60+.
Xavier A. Conlan, John S. Fletcher, Nicholas P. Lockyer and John C. Vickerman
J. Phys. Chem. B 114 (2010) 5468-5479
24 A new SIMS paradigm for 2D and 3D molecular imaging of bio-systems.
John S. Fletcher and John C. Vickerman
Anal. Bioanal. Chem. 396 (2010) 85-104
23 A comparison of PCA and MAF for ToF-SIMS image interpretation.
Alex Henderson, John S. Fletcher, John C. Vickerman
Surf. Interface Anal. 41 (2009) 666-674
22 Explanatory multivariate analysis of ToF-SIMS spectra for the discrimination of bacterial isolates.
Seetharaman Vaidyanathan, John S. Fletcher, Roger M. Jarvis, Alex Henderson, Nicholas P. Lockyer, Royston Goodacre and John C. Vickerman
Analyst 134 (2009) 2352-2360
21 Cellular imaging with secondary ion mass spectrometry.
John S. Fletcher
Analyst 134 (2009) 2204-2215
20 Uncovering new challenges in bio-analysis with ToF-SIMS.
John S. Fletcher, Alex Henderson, Gregory X. Biddulph, Seetharaman Vaidyanathan, Nicholas P. Lockyer and John C. Vickerman
Applied Surface Science 255 (2008) 1264-1270
19 Exploratory analysis of TOF-SIMS data from biological surfaces.
Seetharaman Vaidyanathan, John S. Fletcher, Alex Henderson, Nicholas P. Lockyer and John C. Vickerman
Applied Surface Science 255 (2008) 1599-1602
18 Substrate effects on the analysis of biomolecular layers using Au+, Au3 + and C60 + bombardments.
Jeanette Kordys, John S. Fletcher, Nicholas P. Lockyer and John C. Vickerman
Applied Surface Science 255 (2008) 890-892
17 TOF-SIMS investigation of Streptomyces coelicolor, a mycelial bacterium.
Seetharaman Vaidyanathan, John S. Fletcher, Nicholas P. Lockyer and John C. Vickerman
Applied Surface Science 255 (2008) 922-925
16 A New Dynamic in Mass Spectral Imaging of Single Biological Cells.
John S. Fletcher, Sadia Rabbani, Alex Henderson, Paul Blenkinsopp, Steve P. Thompson, Nicholas P. Lockyer, and John C. Vickerman
Analytical Chemistry 80 (2008) 9058-9064
15 Subsurface Biomolecular Imaging of Streptomyces coelicolor Using Secondary Ion Mass Spectrometry.
Seetharaman Vaidyanathan, John S. Fletcher, Roy Goodacre, Nicholas P. Lockyer, Jason Micklefield, and John C. Vickerman
Analytical Chemistry 80 (2008) 1942-1951
14 Properties of C84 and C24H12 Molecular Ion Sources for Routine TOF-SIMS Analysis.
Biddulph, Gregory X.; Piwowar, Alan M.; Fletcher, John S.; Lockyer, Nicholas P.; Vickerman, John C.
Analytical Chemistry 79 (2007) 7259-7266
13 TOF-SIMS 3D Biomolecular Imaging of Xenopus laevis Oocytes Using Buckminsterfullerene (C60) Primary Ions.
Fletcher, John S.; Lockyer, Nicholas P.; Vaidyanathan, Seetharaman; Vickerman, John C.
Analytical Chemistry 79 (2007) 2199-2206
12 TOF-SIMS Analysis Using C60. Effect of Impact Energy on Yield and Damage.
Fletcher, John S.; Conlan, Xavier A.; Jones, Emrys A.; Biddulph, Greg; Lockyer, Nicholas P.; Vickerman, John C.
Analytical Chemistry 78 (2006) 1827-1831
11 Molecular depth profiling of organic and biological materials.
Fletcher, John S.; Conlan, Xavier A.; Lockyer, Nicholas P.; Vickerman, John C.
Applied Surface Science 252 (2006) 6513-6516
10 ToF-SIMS studies of Bacillus using multivariate analysis with possible identification and taxonomic applications.
Thompson, C. E.; Ellis, J.; Fletcher, J. S.; Goodacre, R.; Henderson, A.; Lockyer, N. P.; Vickerman, J. C.
Applied Surface Science 252 (2006) 6719-6722
9 A comparative study of secondary ion yield from model biological membranes using Aun+ and C60+ primary ion sources.
Baker, M. J.; Fletcher, J. S.; Jungnickel, H.; Lockyer, N. P.; Vickerman, J. C.
Applied Surface Science 252 (2006) 6731-6733
8 ToF-SIMS analysis of bio-systems: Are polyatomic primary ions the solution?
Jones, Emrys A.; Fletcher, John S.; Thompson, Charlotte E.; Jackson, Dean A.; Lockyer, Nicholas P.; Vickerman, John C.
Applied Surface Science 252 (2006) 6844-6854
7 Rapid discrimination of the causal agents of urinary tract infection using ToF-SIMS with chemometric cluster analysis.
Fletcher, John S.; Henderson, Alexander; Jarvis, Roger M.; Lockyer, Nicholas P.; Vickerman, John C.; Goodacre, Royston.
Applied Surface Science 252 (2006) 6869-6874
6 C60, Buckminsterfullerene: its impact on biological ToF-SIMS analysis.
Fletcher, John S.; Lockyer, Nicholas P.; Vickerman, John C.
Surface and Interface Analysis 38 (2006) 1393-1400
5 ToF-SIMS Studies of Sulfuric Acid Hydrate Films.
Fletcher, John S.; Henderson, Alex; Horn, Andrew B.; Vickerman, John C.
Journal of Physical Chemistry B 108 (2004) 5960-5966
4 ToF-SIMS analysis of atmospherically relevant sulphuric acid hydrate films and reactions thereof.
Fletcher, J. S.; Vickerman, J. C.
Applied Surface Science 231-232 (2004) 524-527
3 First detection of molecular hydrate complexes in sulfuric acid aerosols.
Couling, Suzanne B.; Fletcher, John; Horn, Andrew B.; Newnham, David A.; McPheat, Robert A.; Williams, R. Gary.
Physical Chemistry Chemical Physics 5 (2003) 4108-4113
2 Identification of surface molecular hydrates on solid sulfuric acid films.
Couling, Suzanne B.; Nash, Karen L.; Fletcher, John; Henderson, Alex; Vickerman, John C.; Horn, Andrew B.
Journal of the American Chemical Society 125 (2003) 13038-13039
1 The role of surface molecular hydrates in the heterogeneous interaction of NH3 with sulfuric acid monohydrate.
Nash, Karen L.; Sayer, Robert M.; Couling, Suzanne B.; Fletcher, John; Henderson, Alex; Vickerman, John C.; Horn, Andrew B.
Physical Chemistry Chemical Physics 5 (2003) 5101-5107

 

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