RAPID: Rapid and Point-of-Care Electrical Detection of COVID-19 RNA

当前，新型冠状病毒肺炎（COVID-19）大流行及其再次发生，对公共卫生、经济和国家安全构成巨大威胁。为了应对这一紧急情况，需要一种快速、准确且可在现场（医生办公室、医院、机场等）大规模部署的测试方法。通常情况下，COVID-19检测每天需要几个小时，因为它涉及将患者的样本发送到数量有限的认证实验室或疾病控制与预防中心（CDC）。此外，目前的新冠病毒检测能力明显低于预期能力，这一点非常令人担忧。为了解决这一问题，本项目提出了一种变革性检测技术，可以在不到十分钟的时间内，在小于人类拇指大小的硅芯片测试试剂盒上快速、便携、直接地检测COVID-19 RNA，具有高灵敏度和特异性。这些硅芯片测试套件可以使用标准成熟的CMOS技术经济高效地批量生产。RAPID项目的成功将对当前美国乃至全球的COVID-19大流行环境产生变革性影响。该技术可以在1平方厘米的硅芯片上，在不到10分钟的时间内直接和电地检测单个COVID-19 RNA分子。将使用30-mer COVID-19 RNA的特定序列t寡核苷酸作为靶分子。许多单t寡分子将夹在两个金功能化的金属纳米颗粒之间。一个金属纳米粒子与一个负极接触，另一个金属纳米粒子与一个正极接触，在两个电极之间提供电通路。两个电极之间的电压偏置将产生电流，从而实现对单个t寡核苷酸分子的直接电检测。这种对COVID-19 RNA的直接电检测将在直径约100 nm的圆形纳米孔中进行，该纳米孔可作为独立的COVID-19 RNA检测器。将制作一个1平方厘米的新冠病毒检测试剂盒，可容纳25亿个纳米孔新冠病毒探测器。单个检测试剂盒上的大量检测器能够高度灵敏和快速地检测单个COVID-19 RNA分子。此外，RNA检测一直依赖于耗时的逆转录聚合酶链反应（RT-PCR）技术。该方法直接检测单个靶RNA分子，不需要逆转录和PCR扩增反应，使检测结果更加敏感和特异。该技术将在其他传染病、基础生物医学研究、药物开发和早期疾病诊断方面得到广泛应用。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The current pandemic of Coronavirus (COVID-19) and its reoccurrence is a great threat to public health, the economy, and national security. To cope with this emergency, there is a need for a testing method that is rapid, accurate, and deployable in the field (doctor’s offices, hospitals, airports, etc.) at a large scale. Typically, a COVID-19 test takes several hours day as it involves sending the patient’s sample to a limited number of certified labs or the Centers for Disease Control and Prevention (CDC). In addition, it is extremely alarming that the current capacity of COVID-19 testing is significantly lower than the desired capacity. To address this situation, this project proposes a transformative detection technique that enables rapid, portable, and direct electrical detection of COVID-19 RNA in less than ten minutes on a silicon chip test kit smaller than the size of an average human thumb with high sensitivity and specificity. These silicon chip test kits can be cost-effectively mass-produced using standard well-established CMOS technology. The success of this RAPID RAPID project will have a transformative impact in the present COVID-19 pandemic environment not only in U.S. but also globally.The proposed technique offers detection of single COVID-19 RNA molecules directly and electrically in less than 10 minutes on a one square centimeter Si chip. A specific sequence T-oligo of 30-mer COVID-19 RNA will be used as the target molecule. Numerous single T-oligo molecules will be sandwiched between two Au functionalized metal nanoparticles. One metal nanoparticle will be in contact with a negative electrode and the other metal nanoparticle with a positive electrode, providing electrical paths between the two electrodes. A voltage bias between the two electrodes will produce an electrical current, thereby enabling direct electrical detection of single T-oligo molecule. This direct electrical detection of COVID-19 RNA will occur in a circular nanowell of ~100 nm diameter, which acts as an independent COVID-19 RNA detector. One COVID-19 test kit of one square centimeter will be made to accommodate two and half billion nanowell COVID-19 detectors. This enormous number of detectors on a single test kit enables a highly sensitive and rapid detection of single COVID-19 RNA molecules. Furthermore, RNA detection has been relying on time-consuming technique of reverse transcription polymerase chain reaction (RT-PCR). In the proposed approach single target RNA molecules will be directly detected without reverse transcription and PCR amplification reaction there by expending the test results with more sensitivity and specificity. The technique will have extended applications in other infectious diseases, fundamental biomedical research, pharmaceutical drug development, and early disease diagnosis.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.