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

显微镜用于临床诊断，以分析组织，检查血细胞，并确定或分析致病微生物。虽然也经常使用称为“流式细胞仪”的细胞测量仪器，但对于许多临床领域，细胞和组织（例如红细胞和白色血细胞）的分析仍然依赖于专业的实验室工作人员，他们使用基于复杂光学的传统显微镜，设计用于眼睛的视觉检查。同样，临床和诊断微生物学仍然严重依赖于40至135年前的工具，如琼脂平板。抗生素耐药性测试使用浸泡在抗生素中的纸片进行“纸片扩散”试验，自弗莱明首次发现青霉素以来几乎没有变化。有许多原因，旧的技术（光学显微镜）和技术（琼脂板）仍然使用。专家通常已经接受过培训，很难用自动化或电子系统取代专家。快速变化的另一个主要障碍是，运行当前常规测试所需的材料通常非常便宜（培养皿，载玻片，琼脂和肉汤培养基，微孔板），实验室已经配备（光学显微镜，培养箱，移液管，高压灭菌器，光谱仪）。因此，只有当我们开发出真正低成本的方法来复制传统的人类方法，如显微镜分析或微生物学实验室测试时，临床诊断的最大革命才会发生。一个很好的例子，消费电子产品已经使数百年的老技术多余的是在数字显微镜。微型CMOS传感器--价格便宜，因为消费者购买了数百万部智能手机--结合廉价的塑料镜头--为DVD播放器等大众市场产品开发--可以在没有显微镜物镜和试管的情况下放大细菌。这一技术革命可以使用“智能手机显微镜”来展示，它可以由3D打印部件制成，甚至可以由更简单的激光切割有机玻璃或胶合板框架制成。同样，价值30英镑的Raspberry Pi单板计算机可以转变为高功率数字显微镜。在未来十年内，低成本数字显微镜有望彻底改变各种临床诊断。旅行目的此次海外旅行资助将资助参观新加坡国立大学著名的生物医学工程系的BIGHEART生物医学技术研究所，向领先的研究人员学习，并获得光学，电子和软件开发方面的新专业知识。这将补充申请人Edwards之前在基础生物医学科学、微流体临床诊断和医疗创新方面的专业知识。目标临床应用：钩端螺旋体病细菌和血小板新的数字显微镜设备将针对与申请人最近和正在进行的研究相关的两个临床应用。爱德华兹的小组最近展示了在非常低成本的微流体设备中进行细菌检测，识别和抗生素耐药性测试，以及智能手机检测;这项研究继续由2018年初授予的另一项EPSRC资助。爱德华兹还与阅读心血管和代谢研究所（ICMR）的心血管疾病专家密切合作，研究测量血小板功能的新方法。第一个目标是钩端螺旋体病-导致韦氏病-被选中，因为它说明了地球仪临床微生物学家面临的许多共同特征挑战。第二个目标是测量血小板-与ICMR研究相关-非常重要，因为血液凝固是大多数心血管疾病背后的关键过程。将开发先进的低成本数字显微镜技术的新应用，以解决东南亚地区，英国和全球面临的临床挑战。

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.