Ian S Gilmore oral presentation (OB3-Mon2-1-1)
Study of drug uptake and action on metabolic processes at the single-cell level using the 3D OrbiSIMS
1 NPL, Hampton Road, TW11 0LW Teddington, United Kingdom
2 GlaxoSmithKline, Gunnels Wood Rd, SG1 2NY Stevenage, United Kingdom
A major quest for the pharmaceutical industry is the reduction of late-stage drug failure. Measurements that can identify future failure at the early stages of drug development are therefore of great importance. This requires label-free imaging of the distribution of pharmaceutical compounds and metabolites with subcellular resolution. We have previously shown  that ToF-SIMS can provide useful sub-cellular resolution images but analysis is limited by insufficient mass accuracy, mass resolving power for accurate identification of metabolites and sensitivity.
We have recently led the development of a powerful new hybrid instrument, the 3D OrbiSIMS , 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 micrometre resolution argon cluster ion beam for biomolecular imaging and 3D analysis of organics and an ultra-high resolution Bi cluster focussed ion beam with < 200 nm resolution.
In this study, we demonstrate the unparalleled ability for 2D and 3D metabolite imaging with sub-cellular resolution. We show significant variability of drug uptake at the single cell level and demonstrate direct evidence of up regulation of metabolites. This can only be revealed with a single-cell study.
 M.K. Passarelli, C.F. Newman, P.S. Marshall, A. West, I.S. Gilmore, J. Bunch, M. R. Alexander, C. T. Dollery, Analytical chemistry 87 (13), 2015, 6696-6702
 M.K. Passarelli, A. Pirkl, R. Moellers, D. Grinfeld, F. Kollmer, R. Havelund, C.F. Newman, P.S. Marshall, H. Arlinghaus, M. R. Alexander, A. West, S. Horning, E. Niehuis, A. Makarov, C. T. Dollery and I.S. Gilmore, submitted.