Developing a Rapid, Simple-to-use Sensory Platform for Detection of Ultralow Concentration of SARS-CoV-2 Viral Particles Enabled by Electrophoretic Enhancement and Redox Cycling

摘要： 由严重急性呼吸综合征冠状病毒2型引起的新冠肺炎仍然是一种 现代史上罕见的全球卫生危机。满足临床诊断检测需求的余地 一项尚未得到满足的全球挑战。因此，迫切需要简单易用、敏感和快速的诊断方法 感染的早期诊断。这项研究的目标是设计和演示一种 新型低成本、易用的电化学传感平台，实现快速、超灵敏、准确 唾液中SARS-CoV-2病毒粒子的检测(准确率≥为90%，总检测时间为30分钟)。 我们建议通过两种互补的信号放大方案来实现高灵敏度，通过 病毒-磁性纳米颗粒(MNP)偶联物的小电压电泳法浓缩 一组具有亚微米间距的电极，通过氧化还原循环放大电化学电流 在同一组电极之间。重要的是，拟议的平台适合通过以下方式商业化 利用低成本和可扩展的制造方法来制造传感器阵列，而无需使用昂贵和 不可扩展的纳米制造技术。 快速、灵敏和准确的病毒颗粒检测能够更好地监测和控制病毒的传播 感染。建议的平台简单易用，并适合于护理点应用，因为 繁琐的RNA提取步骤，就像RT-PCR方法一样。它可以通过创建传感器来实现高通量测试 阵列在同一芯片上，占地面积小，可同时分析大量样品液滴。这个 建议的感官平台也可以扩展到检测其他传染性病原体，包括登革热和 流感病毒、细菌病原体等。

Abstract: COVID-19 caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) remains an extraordinary global health crisis in the modern history. Meeting the testing needs for clinical diagnosis remains an unmet global challenge. Simple-to-use, sensitive, and rapid diagnostics are therefore urgently needed for early diagnosis of infection. The objective of this research is to design and demonstrate proof-of-principle of a novel low-cost and simple-to-use electrochemical sensing platform to enable rapid, ultrasensitive and accurate detection of SARS-CoV-2 virions in saliva (with accuracy ≥ 90% and total assay time < 30 min). We propose to achieve high sensitivity through two complementary signal amplification schemes, by electrophoretic concentration of virus-magnetic nanoparticle (mNP) conjugates by applying a small voltage on a set of electrodes with sub-micrometer gap, and amplifying electrochemical current through redox cycling between the same set of electrodes. Importantly, the proposed platform is suitable for commercialization by leveraging a low-cost and scalable fabrication method to create the sensor arrays without using expensive and non-scalable nanofabrication techniques. Fast, sensitive, and accurate detection of viral particles enables better surveillance and control of spread of the infection. The proposed platform is simple-to-use and suitable for point-of-care applications by eliminating tedious RNA extraction steps as in RT-PCR methods. It can enable high-throughput testing by creating sensor array on the same chip with small footprint to simultaneously analyze a multitude of sample droplets. The proposed sensory platform can also be expanded to detect other infectious pathogens, including Dengue and Influenza viruses, bacterial pathogens, etc.