Invited Paper AS-MoA1
Cluster Primary Ion Beams Advance the Capability of Bio-Molecule Analysis by SIMS

Monday, October 15, 2007, 2:00 pm, Room 610

The analysis of bio-molecular systems using SIMS with atomic primary ion beams has been bedevilled by three principal limitations - the static limit, the inability to sputter large molecules intact and the very low ionisation probability. The static limit, imposed because of the extensive bombardment induced chemical damage generated by high energy atomic primary ions, limits the amount of material accessible for analysis to 1% of the surface layer, greatly limiting detection sensitivity, the pixel size that can be usefully imaged and eliminating the possibility of molecular depth profiling. Atomic primary ions do not appear to be capable of sputtering intact organic molecules molecular weight much above 500 daltons in significant quantities. This places a major limitation on the value of SIMS in bioanalysis. Finally in common with all desorption mass spectrometries, the ionisation probability of the sputtered species is usually well below 10^-3, placing a further limitation on detection sensitivity and the useful minimum pixel size in SIMS imaging. It is clear that making progress into lifting some or all of these limitations would have a dramatic effect on the value of SIMS in bio-analysis. Over the last 10 years the possibility that cluster primary ion beams would lift some of these limitations has been increasingly investigated. The capability of liquid metal ion sources to generate cluster ions such as Au_n⁺ and Bi_n⁺ has been exploited.^1,2 Gas sources have been used to deliver SF₅⁺ and C₆₀⁺ ions.^3,4 It has been shown that these ions can greatly increase the yield of higher mass ions by orders of magnitude and enable ions up to ~3000 daltons to be detected. Nevertheless the metal cluster ions still generate significant bombardment induced chemical damage such that the static limit is still necessary.⁵ However the larger cluster ions such as C₆₀⁺ generate far less bombardment induced chemical damage and for many systems the static limit can be lifted.⁵ This greatly increases the potential for high sensitivity analysis, imaging with sub-micron resolution and most significant - molecular depth profiling.⁶ This latter development offers the possibility of 3D molecular imaging of bio and organic systems.⁷ This paper will review the progress that has been made and will suggest that to fully exploit the benefits of cluster primary ions new approaches to analysis may be required.

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⁴D.E. Weibel, S. Wong, N.P. Lockyer, P. Blenkinsopp, R. Hill, J.C. Vickerman, Anal. Chem. 75 (2003) 1754-1764
⁵E.Jones, N.P. Lockyer and J.C. Vickerman, Int J, Mass Spectrom., 260 (2007) 146-157
⁶J. Cheng, A. Wucher and N. Winograd, J. Phys. Chem. B 110, 8329-8336 (2006).
⁷J. S. Fletcher, N. P. Lockyer, S. Vaidyanathan, and J. C. Vickerman, Anal. Chem., 79 (2007) 2199-2206