The National Physical Laboratory (NPL), working with major pharmaceutical company GlaxoSmithKline, has initiated a project called 3D nanoSIMS to develop a label-free molecular imaging instrument with unmatched spatial resolution, capable of measuring the intracellular drug distribution.
At present, imaging techniques cannot image beyond micron resolution without adding special chemical labels to the drug molecule. Unfortunately, these labels can significantly affect the drug’s behaviour giving too much uncertainty in the image. This project aims to provide label-free molecular imaging in 3D through enhancing imaging sensitivity by 100 times and increasing the spatial resolution to 50nm.
3D nanoSIMS project will provide high-resolution label-free imaging to reliably see where drugs go to in cells for the first time.
Currently, one of the major challenges to the pharmaceutical industry is the measurement of the intracellular drug concentration. This powerful new instrument could help identify where drugs go at the cellular level, even within specific organelles, answering long-standing questions about whether drug concentration 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.
The new instrument will be based at The UK’s National Centre of Excellence in Mass Spectrometry Imaging (NiCE-MSI), established by NPL and the University of Nottingham.
Professor Ian Gilmore from NPL says: “This project represents significant EU and UK investment in the UK’s already thriving life sciences sector, and emphasises NPL’s expertise in this field. There is no technology in the world at the moment that can achieve what this project aims to do. The new instrument will provide an unprecedented understanding of how different drugs work within cells- helping to assess the efficiency of current drugs and develop better ones in the future.”
Sir Colin Dollery (adviser to the Chairman of Research and Development and on the Global Safety Board at GlaxoSmithKline) comments “GlaxoSmithKline scientists are looking forward to the opportunities the new equipment will provide to explore in detail the sites of action of novel drug molecules within single cells. Designing drugs that are specific for molecular targets is part of drug development but knowing that they reach their target molecule in the right amount at the right place in the right cells is only just beginning to be attainable in intact cells within tissues. This ability will be a great opportunity.”
The project will receive over £4.5M of funding from the Strategic Capability Programme of the National Measurement System of the UK Government’s Department of Business, Innovation and Skills.
The project brings together ION-TOF, a leading manufacturer of mass spectrometers for imaging, with Professors Morgan Alexander, Martyn Davies and Clive Roberts at the University of Nottingham School of Pharmacy and Professor Luke Hanley; Professor and Head of Chemistry Department, University of Illinois at Chicago. ION-TOF will build the revolutionary new instrument which incorporates the powerful Thermo ScientificTM Orbitrap(™) mass analyser for high-performance identification of substances.
As well as enabling new drugs and medicines research, this novel instrument will have important benefits to other fields including for example biomaterials, medical devices, regenerative medicine and next generation plastic electronics for displays.
