RAPID: Development of a New Test for SARS-CoV-2 using Single Molecule Surface Enhanced Raman Spectroscopy

非技术描述：在CoVid-19大流行期间，最具挑战性的方面之一是缺乏检测和追踪感染的测试，以及实施谨慎重新开放国家和经济活动的战略。缺乏检测导致了公共卫生政策的不确定性。检测不仅对于诊断是必要的，而且对于追踪以控制大流行也是必要的。这项工作是基于非传统的技术，用于检测感染患者的病毒。该项目将根据物理学的进步和对光与物质相互作用的量子力学方面的理解，开发一种替代方法。该技术将基于纳米技术和固态物理学的最新发现，从而能够开发光谱技术来检测SARS-Cov-2病毒。该方法被命名为单分子表面增强拉曼光谱（SM-SERS），如果成功，将允许一种快速，廉价，更精确和可靠的方法来检测感染。该方法是基于检测参与细胞感染的病毒的S蛋白。SM-SERS检测一个蛋白质分子的能力将允许早期检测感染和随访从疾病中恢复的患者。此外，对SM-SERS数据的进一步分析将有助于了解病毒蛋白的变化，并有助于开发抗病毒药物。技术描述：在CoVid-19大流行期间，最具挑战性的方面之一是缺乏检测和追踪感染的测试。检测包在数量和质量上的限制导致了公共卫生政策的不确定性。检测不仅对于诊断是必要的，而且对于追踪以控制大流行也是必要的。增加现有测试包数量的实际困难包括，除其他外，难以生产测试所需的化学品。最常用的测试，技术上称为RT-qPCR，成本高，周转时间长，尽管它高度敏感，但会产生许多假阴性，并且基于生物化学方法。本工作是基于拉曼光谱在其SM-SERS模式。该方法是基于放大的非弹性散射光的金属纳米粒子上的局部表面等离子体。主要目标将是建立一个拉曼签名的刺突糖蛋白的SARS-CoV-2病毒，可用于开发检测测试。PI小组先前的研究表明，基于唾液酸化糖蛋白分析的检测具有高灵敏度、特异性和低假阴性率。该项目将开发一种新型的等离子体纳米颗粒与离子液体相结合，这将改善纳米颗粒向含有病毒的溶液的输送。第二个兴趣将是研究精细峰结构，这与蛋白质的形态变化有关。这将有助于抗病毒药物的开发和对病毒生物学的基本了解。该基金会资助的研究将开发一种新的病毒测试方法，资金来自数学和物理科学理事会材料研究部凝聚态物理计划管理的CARES法案。该基金会反映了NSF的法定使命，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，认为值得支持。

Nontechnical Description: During the CoVid-19 pandemic, one of the most challenging aspects is the lack of testing to detect and trace infections and implementing a strategy to carefully re-open the country and economic activity. The lack of testing has resulted in uncertainties about public health policies. Testing is necessary not only for diagnosis but also for tracking to control the pandemic. This work is based on non-traditional techniques for the detection of virus in infected patients. The project will develop an alternative method based on the advances of physics and understanding of the quantum mechanical aspects of interaction of light with matter. The technique will be based on recent discoveries in nanotechnology and solid-state physics, allowing the development of spectroscopy techniques to detect the SARs-Cov-2 virus. The method, named Single Molecule Surface Enhanced Raman Spectroscopy (SM-SERS), If successful, will allow a fast, inexpensive, and much more precise and reliable method to detect infections. The method is based on the detection the S proteins of the virus, which participate in the cell infection. The ability of SM-SERS to detect down to one molecule of protein will allow early detection of infection and follow up of patients who recover from the illness. In addition, further analysis of the SM-SERS data will help to understand changes on the virus proteins and can help in the development of antiviral drugs.Technical Description:During the CoVid-19 pandemic, one of the most challenging aspects has been the lack of testing to detect and trace infections. The limitations in quantities and quality of test kits have resulted in uncertainties about public health policies. Testing is necessary not only for diagnosis but also for tracking to control the pandemic. The practical difficulties to increase the number of available test kits involve, among other things, difficulty in production of the chemicals needed for the test. The most used test, technically known as RT-qPCR, is costly, has a long turnaround time and, although it is highly sensitive, produces many false negatives and are based on biochemical methods. This work is based on the Raman spectroscopy in its SM-SERS modality. The method is based on amplification of the inelastically scattered light by localized surface plasmons on metal nanoparticles. The main goal will be to establish a Raman signature of the spike glycoprotein of the SARS-CoV-2 virus that can be used to develop a detection test. Previous research in the PI's group indicates that tests based on analysis of sialylated glycoproteins have high sensitivity, specificity, and low percentage of false negatives. The project will develop a new type of plasmonic nanoparticles combined with ionic liquids that will improve the nanoparticle delivery to solutions containing the virus. A second interest will be to study the fine peak structure, which is related to morphological changes in the proteins. This will be useful for development of antiviral drugs and the basic understanding of the biology of the virus.This Rapid Response Research (RAPID) grant supports research that will develop a new method for viral testing with funding from the CARES Act managed by the Condensed Matter Physics Program in the Division of Materials Research of the Mathematical and Physical Sciences Directorate.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.