| AVS 63rd International Symposium & Exhibition | |
| Applied Surface Science | Monday Sessions |
| Session AS+BI-MoA |
| Session: | Practical Surface Analysis I: Advancing Biological Surface Analysis/Imaging Beyond ‘Show and Tell’ |
| Presenter: | Ian S. Gilmore, National Physical Laboratory, UK |
| Authors: | I.S. Gilmore, National Physical Laboratory, UK M.K. Passarelli, National Physical Laboratory, UK A. Pirkl, ION-TOF GmbH, Germany R. Moellers, ION-TOF GmbH, Germany E. Niehuis, ION-TOF GmbH, Germany A.A. Makarov, Thermo Fisher Scientific H.F. Arlinghaus, ION-TOF GmbH, Germany R. Havelund, National Physical Laboratory, UK P.D. Rakowska, National Physical Laboratory, UK A.M. Race, National Physical Laboratory, UK A.G. Shard, National Physical Laboratory, UK A. West, GlaxoSmithKline S. Horning, Thermo Fisher Scientific P. Marshall, GlaxoSmithKline M.R. Alexander, The University of Nottingham, UK C.T. Dollery, GlaxoSmithKline |
| Correspondent: | Click to Email |
SIMS has become an important technique for the surface analysis of biological materials. However, critical challenges have hampered the uptake into the life-science industry and biomedical discovery. To succeed in this important sector, it has to progress beyond “Show and Tell”. Biological samples have complex chemistry and an extraordinarily large dynamic range of concentration. The present state-of-the-art struggles to identify unknowns owing to insufficient mass resolving power and mass accuracy of time-of-flight analysers. The situation is further complicated by sample form and vacuum compatibility.
To address this issue, we have developed a powerful new hybrid SIMS instrument combining an OrbitrapTM-based Thermo ScientificTM Q ExactiveTM HF instrument and a dedicated ToF-SIMS 5. The instrument is equipped with high-resolution ion beams including a new micron resolution argon cluster ion beam for biomolecular imaging and 3D analysis of organics and an ultra-high resolution Bi cluster focussed ion beam with < 80 nm resolution. The ToF analyser allows high-speed imaging needed for 3D analysis and the High Field Orbitrap analyser allows high mass resolution, mass accuracy and MS/MS for chemical identification. The instrument is designed for life-sciences applications including sub-cellular 3D imaging of metabolites, imaging of bacteria and biofilms and imaging of medical devices with complex topographies that confound traditional instrument designs.
We show data demonstrating the unique advantages of this novel instrument. Imaging with large argon clusters provides rich biomolecular spectra including intact lipids and metabolites. Existing state-of-the-art instruments are limited to a mass resolving power of around 6,000 which is insufficient to allow unique identification. We show images of mouse brain with a sub-cellular spatial resolution of less than 2 microns simultaneously with a mass resolving power of over 100,000 for intact lipids. We fully separate the (3'-sulfo)Gal-Cer(d18:1/24:1(2-OH)) and (3'-sulfo)Gal-Cer(d18:1/25:0) sulfatides, which reveals a difference in spatial distribution. In the low mass region, mass resolving powers of >400,000 are achieved allowing clear separation of the low abundance metabolite dopamine from other peaks. We show the ability to image the drug amiodarone with sub-cellular resolution and show that the mass spectra are not affected by sample topography. The instrument is also equipped with state-of-the-art cryogenic sample preparation specifically designed for high-resolution biological imaging.
All animal studies were ethically reviewed and carried out in accordance with Animals (Scientific Procedures) Act 1986