Infectious diseases are currently a significant cause of morbidity and mortality, with approximately 700 000 deaths each year worldwide.(1) Viruses, bacteria, and fungi have become increasingly resistant to antimicrobial agents, making antimicrobial resistance (AMR) one of the biggest global health challenges humanity has had to face. Recent reports have highlighted the role pandemics may play in exacerbating AMR through the increased use of disinfectants, alcohol-based hand sanitizers, and antiseptic hand wash.(2) Evidence of antibiotic mis-prescribing in hospitalised COVID-19 patients has also been reported, asking a pandemic-induced spike in AMR.(3) Ultimately, the fate of antimicrobial agents and resulting resistant microorganisms is they are discarded into wastewater, entering the environment as sewage, sludge, and treated wastewater. This results in opportunities for further mutation and horizontal gene transfer (HGT).(2) One of the critical challenges in combatting AMR is the availability of low cost, rapid diagnostic tools to provide near-real-time, on-site, ultrasensitive detection, and determination of the etiology of infection (e.g., viral, bacterial, fungal) to understand the susceptibility of the microorganism to antimicrobial therapy. The World Health Organisation established the “Global Antimicrobial Resistance Surveillance System” (GLASS) in 2015 to provide a standardized approach to AMR surveillance and data collection worldwide. GLASS records phenotypic characteristics, for example, observation of bacterial growth under antibiotics, while genetic information is absent. The lack of routine collection of genetic sequence data underpinning the resistance phenotype limits the ability to understand and respond to changes in resistance patterns. Both phenotypic and genotypic methods are ideally needed to supplement each other as part of a more comprehensive AMR surveillance program.(1) There have been various laboratory-based assays developed for both phenotypic and genotypic AMR detection; however, their use for on site measurements remains challenging. In contrast, paper-based devices have shown great promises for point-of-care (POC) diagnostic for on-site environmental monitoring of both phenotypic and genotypic AMR. Due to its cellulose nature, paper has several advantages, including lightweight, low cost, biocompatibility, and disposable after use via combustion, as well as capillary action enabling sample process without external power.(5) All the above makes it an ideal substrate for POC devices. The development of paper-based devices has flourished since 2007 when it was proposed by the Whitesides group(4) for bioassays. They patterned the paper into discrete sections via photolithography, which was then embedded with epoxy-based negative photoresist (SU-8) to create multiple channels. Then the reagents of different bioassays, for example, enzymatic oxidation of iodide to iodine in the presence of the analyte glucose, were spotted and dried in different channels for subsequent diagnostics. The white color of paper provided a clear contrast for colorimetric results, while the capillary action automatically filtered contaminants from the sample, and therefore the result was free from interference. In addition to biosensing, paper-based devices have also been used in sample extraction and purification, replacing the conventional tube-based cell lysis, and is more time- and labor-efficient.(5) Molecular diagnostics can also be integrated onto paper devices for the detection of antimicrobial resistance genes. This can be achieved via molecular amplification such as loop-mediated isothermal amplification (LAMP) to enhance sensitivity. Such LAMP-integrated paper-based devices have shown an ultrasensitivity and specificity for nucleic acid–based detection for both clinical and environmental samples, which is a significant advancement. Reboud et al.(5) detected malaria species in 98% of infected patients from their finger-prick blood samples with paper-based devices. They first extracted malaria DNA from real blood samples via the paper-microfluidic device then carried out the LAMP reaction with reagents introduced into the reaction chamber, followed by a readout with a lateral flow stripe. Both the sensitivity and specificity of the devices were higher than the gold-standard real-time polymerase chain reaction (PCR). As shown in Table 1, paper-based devices have been developed to monitor AMR using phenotypic and genotypic methods and various environmental samples. They offer a rapid and robust detection tool for environmental surveillance even for nonspecialists, which is extremely important and useful in low resource settings such as in low- and middle-income countries. We believe that paper-based devices will provide a rapid sensing platform for near real-time surveillance of AMR and other targets. These results can help to build descriptions of local resistance profiles, which may formulate regional, national or even global monitoring programmes and support the goal of reducing the global One Health burden. The paper-based device can provide complementary genomic understanding to GLASS while transforming environmental monitoring, which has yet to be rolled out in most countries. Furthermore, the advancement of data science, computational approaches such as deep learning, artificial intelligence and the Internet of Things presents opportunities to have semi- or fully automated systems of environmental monitoring that can not only reflect the current local resistance profiles but also provide insight into emerging risks for timely and effective intervention. Dr Zhugen Yang is a faculty member at Cranfield University, UK. His multidisciplinary group is developing rapid and low-cost sensors and devcies for environmental science (e.g., microbial source tracking, antimicrobial resistance), wastewater-based epidemiology (e.g., illicit drugs and COVID-19) and point-of-care diagnostics. He has authored over 60 referred articles and some of his work was featured in Science as well as public media (e.g., BBC). He received a prestigious UK NERC Fellowship and became a faculty member at the University of Glasgow in 2018. He held a postdoc at the University of Cambridge and EU Marie Curie Fellow at the University of Bath and earned his PhD from the University of Lyon (Ecole Centrale) in France. We acknowledge support from a Royal Academy of Engineering Frontier Follow-up grant (FF\1920\1\36) and the UK NERC Fellowship (NE/R013349/2) on paper sensors. This article references 5 other publications.

中文翻译：

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纸质设备作为快速现场监测“超级细菌”的新工具

传染病目前是发病率和死亡率的重要原因，全世界每年约有 70 万人死亡。 (1) 病毒、细菌和真菌对抗菌药物的耐药性越来越强，使抗菌素耐药性 (AMR) 成为全球最大的健康问题之一。人类不得不面对的挑战。最近的报告强调了通过增加使用消毒剂、含酒精的洗手液和抗菌洗手液，大流行可能在加剧 AMR 方面发挥的作用。 (2) 也有报告表明，住院 COVID-19 患者中抗生素处方错误的证据，询问大流行引起的 AMR 峰值。(3) 最终，抗微生物剂和由此产生的耐药微生物的命运是它们被丢弃到废水中，作为污水、污泥和处理过的废水进入环境。这为进一步突变和水平基因转移 (HGT) 带来了机会。 (2) 对抗 AMR 的关键挑战之一是低成本、快速诊断工具的可用性，以提供近实时、现场、超灵敏的检测，并确定感染的病因（例如，病毒、细菌、真菌）以了解微生物对抗微生物治疗的敏感性。世界卫生组织于 2015 年建立了“全球抗微生物药物耐药性监测系统”（GLASS），为全球 AMR 监测和数据收集提供标准化方法。GLASS 记录表型特征，例如，在抗生素下观察细菌生长，而没有遗传信息。缺乏支持抗性表型的基因序列数据的常规收集限制了理解和响应抗性模式变化的能力。作为更全面的 AMR 监测计划的一部分，理想情况下需要表型和基因型方法相互补充。(1) 已经为表型和基因型 AMR 检测开发了各种基于实验室的检测方法；然而，它们用于现场测量仍然具有挑战性。相比之下，纸质设备在现场环境监测表型和基因型 AMR 的即时 (POC) 诊断方面显示出巨大的前景。由于其纤维素性质，纸具有多种优点，包括重量轻、成本低、生物相容性好以及通过燃烧使用后可丢弃，以及毛细管作用，无需外部电源即可进行样品处理。(5) 以上所有使其成为 POC 设备的理想基板。自 2007 年 Whitesides 小组 (4) 提出用于生物测定以来，纸质设备的开发蓬勃发展。他们通过光刻将纸张图案化为离散部分，然后嵌入环氧基负光刻胶 (SU-8) 以创建多个通道。然后不同生物测定的试剂，例如，在分析物葡萄糖存在下将碘化物酶促氧化成碘，在不同的通道中点样并干燥以用于后续诊断。纸的白色为比色结果提供了清晰的对比，而毛细管作用会自动过滤样品中的污染物，因此结果不受干扰。除了生物传感，纸基设备也被用于样品提取和纯化，取代传统的管式细胞裂解，更省时省力。 (5) 分子诊断也可以集成到纸设备上用于检测抗菌素耐药基因。这可以通过分子扩增实现，例如环介导等温扩增 (LAMP)，以提高灵敏度。这种与 LAMP 集成的纸基设备对临床和环境样本的核酸检测显示出超灵敏性和特异性，这是一项重大进步。Reboud 等人 (5) 使用纸质设备从手指刺血样本中检测到 98% 的感染患者的疟疾种类。他们首先通过纸微流体装置从真实血液样本中提取疟疾 DNA，然后用引入反应室的试剂进行 LAMP 反应，然后用横向流动条纹进行读数。该装置的灵敏度和特异性均高于金标准实时聚合酶链反应 (PCR)。如表 1 所示，已经开发出纸质设备来使用表型和基因型方法以及各种环境样本来监测 AMR。它们为环境监测提供了一种快速而强大的检测工具，即使对于非专业人士也是如此，这在资源匮乏的环境中（例如低收入和中等收入国家）极其重要和有用。我们相信纸质设备将为 AMR 和其他目标的近实时监视提供快速传感平台。这些结果有助于建立对当地耐药性概况的描述，这可能会制定区域、国家甚至全球监测计划，并支持减少全球 One Health 负担的目标。这种纸质设备可以为 GLASS 提供互补的基因组理解，同时改变大多数国家尚未推出的环境监测。此外，数据科学、深度学习、人工智能和物联网等计算方法的进步为拥有半自动化或全自动环境监测系统提供了机会，该系统不仅可以反映当前的当地耐药情况，还可以深入了解及时有效干预的新风险。Zhugen Yang 博士是英国克兰菲尔德大学的教员。他的多学科小组正在开发用于环境科学（例如，微生物源追踪、抗菌素耐药性）、基于废水的流行病学（例如，非法药物和 COVID-19）和即时诊断的快速且低成本的传感器和设备。他撰写了 60 多篇被引用的文章，他的一些作品被《科学》和公共媒体（例如 BBC）收录。他获得了著名的英国 NERC Fellowship 并于 2018 年成为格拉斯哥大学的教员。 他曾在剑桥大学和巴斯大学获得欧盟玛丽居里研究员的博士后，并在里昂大学（Ecole中央）在法国。我们感谢皇家工程学院前沿后续资助 (FF\1920\1\36) 和英国 NERC 奖学金 (NE/R013349/2) 对纸质传感器的支持。