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、检查血细胞以及识别或分析致病微生物。虽然称为“流式细胞仪”的细胞测量仪器也经常被使用，但在许多临床领域，对红细胞和白细胞等细胞和组织的分析仍然依赖于专业实验室工作人员，他们使用基于复杂光学系统的传统显微镜，专为肉眼检查而设计。同样，临床和诊断微生物学仍然严重依赖于有40到135年历史的工具，如琼脂平板。抗生素耐药性检测使用浸泡在抗生素中的纸片进行“纸片扩散”检测，这种检测自弗莱明首次发现青霉素以来几乎没有变化。旧的技术(光学显微镜)和技术(琼脂平板)仍然被使用的原因是多方面的。通常情况下，专家已经接受了培训，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，进行当前常规测试所需的材料往往极其便宜(培养皿、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、吸管、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，临床诊断领域才会发生最大的革命。消费电子产品让数百年的技术变得多余的一个很好的例子是数字显微镜。微型cmos传感器之所以便宜，是因为消费者购买了数百万部智能手机，再加上为DVD播放器等大众市场产品开发的廉价塑料透镜，可以在没有显微镜物镜和管子的情况下放大细菌。这场技术革命可以用“智能手机显微镜”戏剧性地展示出来，这种显微镜既可以由3D打印部件制成，也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，GB 30 Raspberry Pi单板计算机可以转变为高功率数字显微镜。在接下来的十年里，低成本的数字显微镜有望为各种临床诊断带来革命性的变化。旅行目的这笔海外旅行补助金将资助访问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。这将补充申请者爱德华兹在基础生物医学科学、微流体临床诊断学和医疗保健创新方面的先前专业知识。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者最近和正在进行的研究相关的两个临床应用。爱德华兹的团队最近通过智能手机检测，在非常低成本的微流控设备中展示了细菌检测、鉴定和抗生素耐药性测试；这项研究继续得到2018年初授予的另一项EPSRC拨款的资助。爱德华兹还与雷丁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--导致韦尔氏病的疾病--之所以被选中，是因为它说明了全球临床微生物学家面临的许多共同的特征挑战。第二个目标是测量血小板--与ICMR研究相联系--很重要，因为凝血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，以应对东南亚地区、英国和世界各地面临的临床挑战。

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.