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SIMS21, Poland 2017 - Ian S Gilmore abstract

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

Ian S Gilmore1, Melissa K Passarelli1, Carla F Newman2, Paulina D Rakowska1, Peter S Marshall2, Andy West2, Colin T Dollery1

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 [1] 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 [2], 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.

[1] 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

[2] 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.