Small cell imaging using smartphones and single-board computing: analysing platelet function and microbial pathogens using consumer optoelectronics

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Microscopes are used in clinical diagnostics to analyse tissue, to examine blood cells, and to identify or analyse disease-causing micro-organisms. Whilst cell measurement instruments called "flow cytometers" are also often used, for many clinical areas analysis of cells and tissue such as red and white blood cells still relies on expert lab workers, who use traditional microscopes based on complex optics, designed for visual examination by eye. Likewise, clinical and diagnostic microbiology still relies heavily on 40- to 135-year old tools such as agar plates. Antibiotic resistance testing uses paper discs soaked in antibiotic to perform 'disc diffusion' assays that have barely changed since Fleming first discovered penicillin. There are many reasons that that old technology (optical microscope) and techniques (agar plates) are still used. Often experts are already trained and it can be hard to replace experts with automated or electronic systems. Another major barrier to rapid change is that the materials needed to run current conventional tests are often extremely cheap (petri dishes, glass slides, agar and broth media, microwell plates) and labs are already equipped (optical microscope, incubator, pipettes, autoclave, spectrometer). The biggest revolutions in clinical diagnostics can therefore only occur when we develop truly low-cost ways to replicate traditional human methods such as microscopic analysis or microbiology lab tests. An excellent example where consumer electronics have made centuries-old technology redundant is in digital microscopy. Miniature CMOS sensors - only cheap because consumers buy millions of smartphones - combined with cheap plastic lenses - developed for mass market products such as DVD players - can magnify bacteria without microscope objectives and tubes. This technology revolution can be demonstrated dramatically using "smartphone microscopes" which can be made either from 3D printed parts, or even simpler laser-cut Perspex or plywood frames. Similarly, the £30 Raspberry Pi single-board computer can be transformed into a high power digital microscope.Over the next decade, low cost digital microscopy promises to revolutionise various clinical diagnostics.Purpose of TravelThis Overseas Travel Grant will fund a visit to the BIGHEART biomedical technology institute at the prestigious Department of Biomedical Engineering at the National University of Singapore, to learn from leading researchers and gain new expertise in optical, electronic and software development. This will complement applicant Edwards' prior expertise in fundamental biomedical science, microfluidic clinical diagnostics, and healthcare innovation.Target clinical applications: Leptospirosis bacteria and blood plateletsThe new digital microscopy devices will be targeted to two clinical applications linked to recent and ongoing research by the applicant. Edwards' group recently demonstrated bacterial detection, identification and antibiotic resistance testing in very low cost microfluidic devices, with smartphone detection; this research continues funded by another EPSRC grant awarded early in 2018. Edwards also works closely with cardiovascular disease experts within Reading's Institute of Cardiovascular and Metabolic Research (ICMR), studying new methods to measure platelet function. The first target is Leptospirosis - which causes Weil's disease - was selected as it illustrates many of the common characteristic challenges faced by clinical microbiologists across the globe. The second target is measurement of platelets - linking with ICMR research - is important because blood clotting is a critical process behind the majority of cardiovascular disease. Novel applications of advanced low-cost digital microscopy technology will be developed that address clinical challenges faced across the SE Asia region, the UK, and worldwide.