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Providing new insights into drug discovery and cell biology

We are working with partners to develop a new high resolution molecular imaging instrument called 3D OrbiSIMS

The need

It costs approximately £1.4 billion to produce a new medicine, but this could be reduced if candidates that fail at late stage were identified earlier. Currently, one of the major challenges is to measure the intracellular drug concentration. As identified in the Maxwell Report, high-resolution molecular imaging of drugs in the body is crucial in improving the effectiveness of drug discovery, by shedding light on fundamental biological processes, and revealing the drug distribution at the cellular level and across the body.

We led a multidisciplinary team including experts in drug discovery at GSK and pharmaceutical science at the University of Nottingham alongside leading mass spectrometry companies, ION-TOF GmbH and Thermo Fisher Scientific to develop 3D OrbiSIMS. This is a revolutionary new label-free molecular imaging instrument with the highest reported simultaneous spatial and mass resolutions. Such high performance is essential to reveal the biomolecular complexity in a single cell.

The impact

The 3D OrbiSIMS could measure drug uptake and effect in single cells and corresponding metabolic changes. It could help identify where drugs go at the cellular level to help 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.

International standards are an important route to impact and we have an established track record that we will build by leading several VAMAS interlaboratory studies, to deliver the standards needed to ease the adoption of the 3d OrbiSIMS around the world.

Advances in the physical sciences and engineering are accelerating a revolution in healthcare. I am delighted that a multidisciplinary team, led by NPL in collaboration with GSK, has made a leap forward in high-resolution molecular imaging, the 3D OrbiSIMS. This powerful new capability allows the detection of drugs and metabolites with sub-cellular resolution, giving us the possibility of determining the precise distribution of a medicine and the effect it has, even within a cell.

John Lepore - Senior Vice President for Pipeline and Discovery at GSK