Moser Nicolas, Yu Ling-Shan, Rodriguez Manzano Jesus, Malpartida-Cardenas Kenny, Au Anselm, Arkell Paul, Cicatiello Chiara, Moniri Ahmad, Miglietta Luca, Wang Wen-Hung, Wang Sheng Fan, Holmes Alison, Chen Yen-Hsu, Georgiou Pantelis
Centre for Bio-Inspired Technology, Department of Electrical and Electronic Engineering, Faculty of Engineering, Imperial College London, London, United Kingdom.
Institute of Biopharmaceutical Sciences, College of Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan.
Front Bioeng Biotechnol. 2022 Sep 15;10:892853. doi: 10.3389/fbioe.2022.892853. eCollection 2022.
Dengue is one of the most prevalent infectious diseases in the world. Rapid, accurate and scalable diagnostics are key to patient management and epidemiological surveillance of the dengue virus (DENV), however current technologies do not match required clinical sensitivity and specificity or rely on large laboratory equipment. In this work, we report the translation of our smartphone-connected handheld Lab-on-Chip (LoC) platform for the quantitative detection of two dengue serotypes. At its core, the approach relies on the combination of Complementary Metal-Oxide-Semiconductor (CMOS) microchip technology to integrate an array of 78 × 56 potentiometric sensors, and a label-free reverse-transcriptase loop mediated isothermal amplification (RT-LAMP) assay. The platform communicates to a smartphone app which synchronises results in real time with a secure cloud server hosted by Amazon Web Services (AWS) for epidemiological surveillance. The assay on our LoC platform (RT-eLAMP) was shown to match performance on a gold-standard fluorescence-based real-time instrument (RT-qLAMP) with synthetic DENV-1 and DENV-2 RNA and extracted RNA from 9 DENV-2 clinical isolates, achieving quantitative detection in under 15 min. To validate the portability of the platform and the geo-tagging capabilities, we led our study in the laboratories at Imperial College London, UK, and Kaohsiung Medical Hospital, Taiwan. This approach carries high potential for application in low resource settings at the point of care (PoC).
登革热是世界上最普遍的传染病之一。快速、准确且可扩展的诊断方法是登革热病毒(DENV)患者管理和流行病学监测的关键,然而目前的技术无法达到所需的临床敏感性和特异性,或者依赖大型实验室设备。在这项工作中,我们报告了我们的与智能手机相连的手持式芯片实验室(LoC)平台用于定量检测两种登革热血清型的转化。该方法的核心是将互补金属氧化物半导体(CMOS)微芯片技术与78×56电位传感器阵列集成在一起,并结合无标记逆转录环介导等温扩增(RT-LAMP)检测法。该平台与智能手机应用程序通信,该应用程序将结果实时与由亚马逊网络服务(AWS)托管的安全云服务器同步,以进行流行病学监测。我们的LoC平台上的检测方法(RT-eLAMP)在使用合成DENV-1和DENV-2 RNA以及从9株DENV-2临床分离株中提取的RNA时,在基于金标准荧光的实时仪器(RT-qLAMP)上表现出相当的性能,在15分钟内实现了定量检测。为了验证该平台的便携性和地理标记功能,我们在英国伦敦帝国理工学院和台湾高雄医学大学医院的实验室中开展了研究。这种方法在资源匮乏的即时医疗(PoC)环境中具有很高的应用潜力。