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

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 Travel
This 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 platelets
The 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.

1 Capacity building in strategically vital interface between digital technology and biomedical science
Whilst many engineers focus on biomedical technology as a vital target application for their research, it is relatively less common for biomedical scientists to move into engineering. Worldwide, there are more engineering and chemical engineering departments with biomedical research strength, than biomedical departments with engineering skills. Applicant Edwards is part of a smaller group of biologists with strong interest and active research in engineering science. To build new long-term research programs at this life science-engineering interface, this OTG will permit the PI to gain new expertise in the areas of optoelectronic and image analysis software engineering, through a long visit to a leading Biomedical Engineering hub.
This new expertise will be brought back to the UK within an appropriate applied science institution and allow PI to continue to bridge the University of Reading's Pharmacy department with the recently founded Bioengineering division. Our capability at the life science - engineering interface must continue to maintain it's world-leading reputation, and a significant proportion of our economy relies on this capacity for interdisciplinary research especially in healthcare.

2 The initial near-term economic impact is most likely to be expanding research capacity supporting R&D investment in the UK research base
Life science research remains one of the UK's greatest assets, with world-leading expertise in fundamental bioscience allied to as much as 20% of GDP in life science industries such as pharma, biotech and medical technology. We have complementary expertise in software, including world-leading reputation in AI. Digital healthcare technology is therefore rightly recognised as a major growth area and a significant focus of strategic research funding. This project will help secure further R&D investment in digital microscopy, a vital interface between cell and microbial biology and digital analysis. Our understanding of the difficult process innovation in healthcare is also vital to deliver disruptive technology into the clinic- many regulatory and health systems barriers to application of digital technology to healthcare remain, but the UK leads the way in understanding these barriers (e.g. through Academic Health Science Networks and Diagnostics Evidence Centres).
Investment in research and innovation in biomedical science is equally important for the UK to build upon its strong life science research base and deliver economic growth. There is great potential for this initial research project to lead to new inventions in hardware, software and in identifying novel application of existing technology. Ultimately this should lead to securing further R&D investment into UK healthcare technology, helping to prove the value of UK research base as a leading biomedical technology development base, and move towards future economic returns from new products.

3 Public and patient benefit
Ultimately, the purpose of this research is to develop new technology that automates clinical diagnostic processes that are currently laborious and manual, specifically in the areas of cardiovascular disease (blood cell measurements) and clinical microbiology (e.g. functional serology or pathogenic bacteria identification). However, this OTG is a new research project and benefits to patients will follow many years later through downstream R&D programs, and are thus hard to quantify directly. Whilst patient benefits are long-term, the pathway to this outcome will generate economic impact (see 2).

4 Public understanding of EPSRC funding
The application of smartphone camera technology to clinical diagnostics is expected to generate significant public interest both in the UK and in SE Asia, especially when coupled to public health problems such as neglected tropical disease or heart attacks.