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采用 CMOS 片上实验室平台进行定量和快速恶性疟原虫疟疾诊断及青蒿素耐药性检测。

Quantitative and rapid Plasmodium falciparum malaria diagnosis and artemisinin-resistance detection using a CMOS Lab-on-Chip platform.

机构信息

Centre for Bio-Inspired Technology, Department of Electrical and Electronic Engineering, Imperial College London, UK.

Centre for Bio-Inspired Technology, Department of Electrical and Electronic Engineering, Imperial College London, UK.

出版信息

Biosens Bioelectron. 2019 Dec 1;145:111678. doi: 10.1016/j.bios.2019.111678. Epub 2019 Sep 7.

Abstract

Early and accurate diagnosis of malaria and drug-resistance is essential to effective disease management. Available rapid malaria diagnostic tests present limitations in analytical sensitivity, drug-resistance testing and/or quantification. Conversely, diagnostic methods based on nucleic acid amplification stepped forwards owing to their high sensitivity, specificity and robustness. Nevertheless, these methods commonly rely on optical measurements and complex instrumentation which limit their applicability in resource-poor, point-of-care settings. This paper reports the specific, quantitative and fully-electronic detection of Plasmodium falciparum, the predominant malaria-causing parasite worldwide, using a Lab-on-Chip platform developed in-house. Furthermore, we demonstrate on-chip detection of C580Y, the most prevalent single-nucleotide polymorphism associated to artemisinin-resistant malaria. Real-time non-optical DNA sensing is facilitated using Ion-Sensitive Field-Effect Transistors, fabricated in unmodified complementary metal-oxide-semiconductor (CMOS) technology, coupled with loop-mediated isothermal amplification. This work holds significant potential for the development of a fully portable and quantitative malaria diagnostic that can be used as a rapid point-of-care test.

摘要

早期、准确的疟疾诊断和耐药性检测对于有效的疾病管理至关重要。现有的快速疟疾诊断测试在分析灵敏度、耐药性检测和/或定量方面存在局限性。相反,基于核酸扩增的诊断方法因其高灵敏度、特异性和稳健性而得到了进一步发展。然而,这些方法通常依赖于光学测量和复杂的仪器,这限制了它们在资源匮乏的即时护理环境中的适用性。本文报告了使用内部开发的片上实验室平台,对世界范围内主要的疟原虫寄生虫疟原虫 falciparum 进行特异性、定量和全电子检测。此外,我们还展示了对与青蒿素耐药性相关的最常见单核苷酸多态性 C580Y 的片上检测。使用在未修改的互补金属氧化物半导体 (CMOS) 技术中制造的离子敏场效应晶体管,结合环介导等温扩增,实现了实时非光学 DNA 传感。这项工作为开发完全便携式和定量的疟疾诊断方法提供了巨大潜力,可作为一种快速即时护理检测手段。

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