Skip to main content
Log in

A new SIMS paradigm for 2D and 3D molecular imaging of bio-systems

  • Review
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

With the implementation of focused primary ion beams, secondary ion mass spectrometry (SIMS) has become a significant technique in the rapidly emerging field of mass spectral imaging in the biological sciences. Liquid metal ion guns (LMIG) offered the prospect of sub-100 nm spatial resolution, however this aspiration has yet to be reached for molecular imaging. This brief review shows that using LMIG the limitations of the static limit and low ionization probability will restrict useful imaging to around 2 μm spatial resolution with high-yield molecules. The only prospect of going beyond this in the absence of factors of 100 increase in ionization probability is to use polyatomic ion beams such as C +60 , for which bombardment induced damage is low. In these cases sub-micron imaging becomes possible, using voxels together with molecular depth profiling and 3D imaging. The discussion shows that conventional ToF-SIMS instrumentation then becomes a limitation in that the pulsed ion beam has a very low duty cycle which results in inordinately long analysis times, and pulsing the beam means that high-mass resolution and high spatial resolution are mutually incompatible. New instrumental configurations are described that allow the use of a dc ion beam and separate the mass spectrometry for the ion formation process. Early results from these instruments suggest that sub-micron analysis and imaging with high mass resolution and good ion yields are now realizable, although the low ion yield issue still needs to be solved.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13
Fig. 14
Fig. 15

Similar content being viewed by others

References

  1. Prewett PD, Mair GLR (1991) Focused ion beams from liquid metal ion sources. Research Studies Press, Taunton

    Google Scholar 

  2. Cliff B, Lockyer N, Jüngnickel H, Stephens G, Vickerman JC (2003) Rap Comm Mass Spectrom 17:2163

    Article  CAS  Google Scholar 

  3. Braun RM, Blenkinsopp P, Mullock SR, Corlett C, Willey KF, Vickerman JC, Winograd N (1998) Rap Comm Mass Spectrom 12:1246

    Article  CAS  Google Scholar 

  4. Ostrowski SG, Van Bell CT, Winograd N, Ewing AG (2004) Science 305:71

    Article  CAS  Google Scholar 

  5. Delcorte A, Garrison BJ (2001) Nucl Inst Methods B 180:37

    Article  CAS  Google Scholar 

  6. Benguerba M, Brunelle A, Della-Negra S, Depauw J, Joret H, Le Beyec Y, Blain MG, Schweikert EA, Ben Assayag G, Sudraund P (1991) Nucl Instr Meth Phys Res B62:8

    Article  CAS  Google Scholar 

  7. Le Beyec Y (1998) Int J Mass Spectrom 174:101

    Article  Google Scholar 

  8. Harris RD, Baker WS, Van Stipdonk MJ, Crooks RM, Schweikert EA (1999) Rapid Commun Mass Spectrom 13:1374

    Article  CAS  Google Scholar 

  9. Harris RD, Van Stipdonk MJ, Schweikert EA (1998) Int J Mass Spectrom Ion Proc 174:167

    Article  CAS  Google Scholar 

  10. Davies N, Weibel DE, Lockyer NP, Blenkinsopp P, Hill R, Vickerman JC (2002) Appl Surf Sci 203-204:223

    Article  Google Scholar 

  11. Wong SCC, Blenkinsopp P, Lockyer NP, Weibel DE, Vickerman JC (2002) Appl Surf Sci 203–204:219

    Google Scholar 

  12. Weibel DE, Wong SCC, Lockyer N, Blenkinsopp P, Hill R, Vickerman JC (2003) Anal Chem 75:1754

    Article  CAS  Google Scholar 

  13. Tomboul D, Kollmer F, Niehuis E, Brunelle A, Laprévote O (2005) J Am Soc Mass Spectrom 16:1608

    Article  Google Scholar 

  14. Szakal C, Kozole J, Garrison BJ, Winograd N (2006) Phys Rev Lett 96:216104

    Article  Google Scholar 

  15. Cheng J, Winograd N (2005) Anal Chem 77:3651

    Article  CAS  Google Scholar 

  16. Sjövall P, Lausmaa J, Johansson B, Andersson M (2004) Anal Chem 76:4271–4278

    Article  Google Scholar 

  17. Nygren H, Borner K, Hagenhoff B, Malmberg P, Mansson JE (2005) Biochim Biophys Acta 1737:102–110

    CAS  Google Scholar 

  18. Touboul D, Brunelle A, Halgand F, De La Porte S, Laprévote O (2005) J Lipid Res 46:1388–1395

    Article  CAS  Google Scholar 

  19. Tahallah N, Brunelle A, De La Porte S, Laprévote O (2008) J Lipid Res 49:438–454

    Article  CAS  Google Scholar 

  20. Debois D, Bralet M-P, Le Naour F, Brunelle A, Laprévote O (2009) Anal Chem 81:2823–2831

    Article  CAS  Google Scholar 

  21. Gillen G, Simons DS, Williams P (1990) Anal Chem 62:2122–2130

    Article  CAS  Google Scholar 

  22. Jones EA, Lockyer NP, Vickerman JC (2007) Int J Mass Spectrom 260:146–157

    Article  CAS  Google Scholar 

  23. Russo MF Jr, Wojciechowski IA, Garrison BJ (2006) Appl Surf Sci 252:6423

    Article  CAS  Google Scholar 

  24. Ryan KE, Wojciechowski IA, Garrison BJ (2007) J Phys Chem C 111:12822

    Article  CAS  Google Scholar 

  25. Cheng J, Wucher A, Winograd N (2006) J Phys Chem B 110:8329–8336

    Article  CAS  Google Scholar 

  26. Gillen G, Fahey A, Wagner M, Mahoney C (2006) Appl Surf Sci 252:6537

    Article  CAS  Google Scholar 

  27. Touboul D, Kollmer F, Niehuis E, Brunelle A, Laprévote O (2005) J Am Soc Mass Spectrom 16:1608

    Article  CAS  Google Scholar 

  28. Vaidyanathan S, Fletcher JS, Goodacre R, Lockyer NP, Micklefield J, Vickerman JC (2008) Anal Chem 80:1942

    Article  CAS  Google Scholar 

  29. Fletcher JS, Lockyer NP, Vaidyanathan S, Vickerman JC (2007) Anal Chem 79:2199

    Article  CAS  Google Scholar 

  30. Breitenstein D, Rommel CE, Möllers R, Wegener J, Hagenhoff B (2007) Angew Chem Int Ed 46:5332

    Article  CAS  Google Scholar 

  31. Nygren H, Hagenhoff B, Malmberg P, Nilsson M, Richter K (2007) Micros Res Tech 70:969–974

    Article  CAS  Google Scholar 

  32. Debois D, Brunelle A, Laprévote O (2007) Int J Mass Spectrom 260:115–120

    Article  CAS  Google Scholar 

  33. Jones EA, Lockyer NP, Vickerman JC (2008) Anal Chem 80:2125–2132

    Article  CAS  Google Scholar 

  34. Cheng J, Winograd N (2005) Anal Chem 77:3651–3659

    Article  CAS  Google Scholar 

  35. Shard AG, Brewer PJ, Green FM, Gilmore IS (2007) Surf Interface Anal 39:294–298

    Article  CAS  Google Scholar 

  36. Sjovall P, Johansson B, Lausmaa J (2006) Appl Surf Sci 252:6966–6974

    Article  Google Scholar 

  37. Piwowar AM, Lockyer NP, Vickerman JC (2009) Anal Chem 81:1040–1048

    Article  CAS  Google Scholar 

  38. Fletcher JS, Henderson A, Biddulph GX, Vaidyanathan S, Lockyer N, Vickerman JC (2008) Appl Surf Sci 255:1264–1270

    Article  CAS  Google Scholar 

  39. Loboda AV, Krutchinsky AN, Bromirski M, Ens W, Standing KG (2000) Rapid Commun Mass Spectrom 14:1047

    Article  CAS  Google Scholar 

  40. Carado A, Passarelli MK, Kozole J, Wingate JE, Winograd N, Loboda AV (2008) Anal Chem 80:7921–7929

    Article  CAS  Google Scholar 

  41. Fletcher JS, Rabbani S, Henderson A, Blenkinsopp P, Thompson SP, Lockyer NP, Vickerman JC (2008) Anal Chem 80:9058–9064

    Article  CAS  Google Scholar 

  42. Makarov AA, Raptakis EN, Derrick PJ (1995) Int J Mass Spectrom Ion Proc 146:165–182

    Article  Google Scholar 

  43. Leggett GJ, Briggs D, Vickerman JC (1991) Surf Interface Anal 17:737–744

    Article  CAS  Google Scholar 

  44. Leggett GJ, Vickerman JC (1992) Int J Mass Spectrom Ion Proc 122:281–319

    Article  CAS  Google Scholar 

  45. Todd PJ, McMahon JM, Short RT (1995) Int J Mass Spectrom Ion Proc 143:131–145

    Article  CAS  Google Scholar 

  46. Wucher A, Sun S, Szakal C, Winograd N (2004) Anal Chem 76:7234

    Article  CAS  Google Scholar 

  47. Conlan XA, Lockyer NP, Vickerman JC (2006) Rapid Commun Mass Spectrom 20:1327

    Article  CAS  Google Scholar 

  48. Wucher A, Cheng J, Winograd N (2007) Anal Chem 79:5529–5539

    Google Scholar 

  49. Jones EA, Lockyer NP, Kordys J, Vickerman JC (2007) J Am Soc Mass Spec 18:1559–1567

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors acknowledge the support of the UK Engineering and Physical Sciences Research Council, Life Sciences initiative.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to John C. Vickerman.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fletcher, J.S., Vickerman, J.C. A new SIMS paradigm for 2D and 3D molecular imaging of bio-systems. Anal Bioanal Chem 396, 85–104 (2010). https://doi.org/10.1007/s00216-009-2986-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-009-2986-3

Keywords

Navigation