A new dynamic in mass spectral imaging for biological systems

A collaborative project is proposed with the Penn State SIMS Group to capitalise on the dramatic advances in ToF-SIMS resulting from the development of routine C60 primary ion beam technology by the Manchester SIMS Group in 2000. ToF-SIMS (Time of Flight Secondary Ion Mass Spectrometry) analyses the surface chemistry of materials by bombarding the surface with moderate energy particles and thereby removing and detecting molecular and atomic fragments in the form of charged particles (or ions). C60 beams remove molecules rather gently ensuring that the analyte materials are much less damaged in the removal process than under the atomic ion beam bombardment technology previously used. C60 also delivers a much larger molecular removal rate (sputtering) resulting in enhanced sensitivity and analytical efficiency. The Penn State Group under Professor Winograd, rapidly recognised the importance of this development and in parallel with the Manchester group has been exploring C60 sputtering and developing applications. The most exciting advance is that because C60 is able to remove surface layers with little damage to underlying layers, molecular depth profiling is possible and, of even more significance, 3D molecular imaging with good 2D and 3D spatial resolution. The potential applications in biological research alone are legion.Both groups have realized that to exploit this new capability requires new instrument concepts. The Manchester group has been funded by EPSRC to develop a new instrument design with two small UK companies. This is close to completion and initial results show that it will more than meet expectations. The Penn State group has been funded to adapt a current commercial mass spectrometer of somewhat different geometry with a C60 source to the same end. The outputs from their system are also beyond expectations. Through discussions at international meetings it is clear that the research and development requirements to fully realise the potential of this SIMS analysis approach are almost identical, but exceed the level envisaged when each groups' work was originally funded. A coordinated programme of work at PSU and UoM is proposed to realise the full power of the new technologies. This will involve the exchange of doctoral and post-graduate student researchers to harness the expertise of the two groups on two focused areas of work. The first will be concerned with fundamental sputtering studies and analysis protocol development to fully enable the potential for reliable 2 and 3 D analysis and imaging. Fundamental studies will seek to unravel and define the degree to which ion/material interactions and instrumental parameters influence the acquisition of reliable and understandable 2D and 3D chemical images. Parallel studies on the two instruments will be vital for this work. The other important operational parameter is that both instruments deliver vast amounts of information very rapidly and the outputs are potentially very complex. Computational methods will be researched to handle the outputs and deliver understandable information quickly, for example using the latest 3D visualisation methods and the use of MVA analysis techniques to extract real chemical information.Sensitivity is the central issue in mass spectrometry in the imaging mode because the desire for increasing levels of spatial resolution means there can never be enough ion yield. The current ionisation probability in organic SIMS (and indeed in other desorption mass spectrometries such as MALDI and DESI) is less than 10-5 in most cases. Increasing secondary ion yield by at least a factor 10 would be an enormous benefit to this and other mass spectrometries. The second area of research will therefore investigate mechanisms and develop equipment to implement enhanced cationisation and particularly protonation of bio-molecules to seek to obtain a more than 10-fold increase.