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

目前冠状病毒(新冠肺炎)的大流行及其复发对公共卫生、经济和国家安全构成极大威胁。为了应对这种紧急情况，需要一种快速、准确且可在现场(医生办公室、医院、机场等)部署的检测方法。规模很大。通常，新冠肺炎检测每天需要几个小时，因为它涉及到将患者的样本送到有限数量的认证实验室或疾病控制和预防中心。此外，新冠肺炎目前的测试能力明显低于预期能力，这一点非常令人担忧。为了解决这种情况，该项目提出了一种革命性的检测技术，可以在小于人类拇指大小的硅芯片检测试剂盒上在不到十分钟的时间内快速、便携和直接电检测新冠肺炎RNA，并具有高灵敏度和特异性。这些硅片测试套件可以使用标准成熟的cmos技术进行经济高效的批量生产。这一快速快速项目的成功将对当前新冠肺炎大流行的环境产生革命性的影响，不仅在美国，而且在全球范围内。该技术可以在不到10分钟的时间内在1平方厘米的硅芯片上直接以电子方式检测到单个新冠肺炎核糖核酸分子。将使用30聚体新冠肺炎核糖核酸的特定序列T-寡核苷酸作为靶分子。许多单一的T-寡聚分子将被夹在两个Au功能化的金属纳米颗粒之间。一个金属纳米颗粒将与负电极接触，另一个金属纳米颗粒与正电极接触，在两个电极之间提供电路径。两个电极之间的电压偏置将产生电流，从而实现对单个T-寡聚分子的直接电检测。这种对新冠肺炎核糖核酸的直接电检测将发生在直径约100 nm的圆形纳米孔中，它作为独立的新冠肺炎核糖核酸检测器。将制作一套1平方厘米的新冠肺炎检测试剂盒，以容纳25亿纳米瓦新冠肺炎探测器。单个检测试剂盒上安装了大量检测器，能够高度灵敏和快速地检测单个新冠肺炎核糖核酸分子。此外，RNA的检测一直依赖于耗时的逆转录聚合酶链式反应(RT-PCR)技术。在该方法中，通过将检测结果扩展为更敏感和更特异的方法，可以直接检测单个靶RNA分子，而不需要进行反转录和PCR扩增反应。这项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。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.