Discussion

Mass spectrometry is, arguably, one of the most powerful chemical analytical techniques. Secondary ion mass spectrometry brings this analytical capability to image surfaces and interfaces in 3D with high-sensitivity and with nanoscale depth resolution. Its ability for high-sensitivity analysis has played an important role in the semiconductor industry measuring dopant profile concentrations. The rapid growth of the semiconductor industry is popularly summarised by Moore’s law(1); which shows that over the last five decades the number of transistors in a chip doubles every two years. Recently, Scannell et al (2) show that the reverse is the case for the pharmaceutical industry and the number of drugs per billion dollars of investment has dropped from around 50 to less than 1 over a similar timescale. They call this “Eroom’s” law, Moore’s law in reverse.

Analogously to the semiconductor industry, SIMS could now provide important benefits to the pharmaceutical industry. The challenge here is to measure where drugs go at the cellular level, even within specific organelles, to answer long-standing questions about whether drug concentrations are sufficiently high in the right places to have a therapeutic effect, or if the medicine is lodging within cellular components and causing toxicity. If anomalies were spotted earlier it might help to explain toxicities or lack of efficacy of a medicine and reduce costly late-stage failures (3,4)

To meet this challenge, NPL in collaboration with GlaxoSmithKline, ION-TOF GmbH, Thermo Fisher Scientific and the University of Nottingham is building a revolutionary new instrument, the 3D nanoSIMS (4), which incorporates the powerful Thermo Scientific™ Orbitrap™ mass analyzer for high-performance identification of drugs and metabolites. The stunning capability of SIMS to study drugs in tissue and cells will be highlighted and the characteristics of the new instrument will be outlined. The benefits of combining SIMS with the new generation of ambient mass spectrometry techniques and the rapidly rising challenge of Big Data will also be discussed.

References: [1] Moore, Gordon E.. "Cramming more components onto integrated circuits" (PDF). Electronics Magazine. (1965) [2] Scanwell, J.W., Blanckley, A., Boldon, H., Warrington B., Nat. Rev. Drug Discovery., 11, 191-99 (2012) [3] C T Dollery, Clinical Pharmacology & Therapeutics, (2013); 93, 263–266. [4] The 3D nanoSIMS project, http://www.npl.co.uk/news/3d-nanosims-label-free-molecular-imaging [2013]