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Research AssociateHonorary Lecturerjohn.fletcher @ manchester.ac.uktel: +44 (0)161 306 4440 |
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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.

Ionoptika 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
| 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. (2012) |
| 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 (2011) |
| 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 (2011) ACS ASAP |
| 34 | 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 |
| 33 | 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 |
| 32 | 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 |
| 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 | 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 |
| 29 | 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 |
| 28 | 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 |
| 27 | 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 |
| 26 | 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 |
| 25 | 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 |
| 24 | 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 (2010) ACS ASAP |
| 23 | Cellular imaging with secondary ion mass spectrometry. John S. Fletcher Analyst 134 (2009) 2204-2215 |
| 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 | 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 |
| 20 | 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 |
| 19 | 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 |
| 18 | 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 |
| 17 | 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 |
| 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 | 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 |
| 11 | 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 |
| 10 | 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 |
| 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 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 |
| 7 | 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 |
| 6 | 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 |
| 5 | 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 |
| 4 | 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 |
| 3 | 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 |
| 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 | 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 |

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