Taking super resolution microscopy beyond the laboratory

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In this fellowship, I will build a new portable imaging technology which will allow scientists, medical doctors, conservationists and industrial parties to visualise the smallest building blocks of any biological sample from any location. The UK and other governments are currently making urgent investments into understanding the role of molecules and cells in the "Global Challenges" which include the effects of climate change on food sources and lifestyle effects on major human diseases and ageing. Despite this urgency, we remain unable to visualise the relevant genes, proteins and cellular components in their natural environments or the geographical locations of the problem. Frustratingly, the technology for visualising such minute structures exists. It is called 'super-resolution microscopy' and we even hailed its invention with a Nobel Prize in 2014. However, it has remained beyond the reach of field scientists and clinicians because it has always relied upon specialist skill for its operations and expensive and bulky equipment for its implementation. In this fellowship, I will use a radically new approach to make super-resolution microscopy portable, cheap and easy to use. I will harness a novel chemical reaction which allows any scientists to physically inflate a desired feature of a sample, for example a patient biopsy or a small organism, by 200 to 3000-fold in volume. I will build a set of molecular tools and a miniaturised transparent enclosure within which the desired sample can be inflated under full computer control. With the physical inflation of the sample, its finer features will then become easy to visualise with a simple microscope. To this end, I will build a miniaturised optical microscope which can acquire precise digital images of the cells, tissues or organism which were previously too small to be visualised with traditional optical microscopes. To refine and ensure that this device delivers this claimed imaging capability, I will carry out case studies in partnership with experts whose samples are collected outside of the academic laboratory (in Phase II). They include a field scientist who will use it to examine young sea urchins in the UK coast, doctors and sports scientists who will screen for the fine structure of needle biopsies taken in the clinic from human patients, and a partner of the European space programme who will use it to remotely study the effect 'zero gravity' on the ageing of microscopic worms sent between earth and the international space station. Beyond the timeline of the fellowship, I will develop this technology into a handheld device which will become a part of the repertoire of any scientist, doctor or field surveyor who wishes to study life in the sub-microscopic scale outside of the walls of the laboratory. Applied to the "Global Challenges", this technology will broaden their ability to visualise and target cells and molecules to find the solutions that humankind urgently needs. I apply for this fellowship as the ideal candidate to develop this tool, having acquired 11 years of experience in adopting and refining super-resolution microscopy. This fellowship will provide a critical springboard to developing this transformative technology by affording me (i) an interdisciplinary skill base required for building the tool and (ii) the opportunity to partner with the end-users of the technology throughout the complete programme of tool building and field testing.