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

RAPID：使用单分子表面增强拉曼光谱开发 SARS-CoV-2 新测试

• 批准号: 2030488
• 负责人: Miguel Jose Yacaman
• 金额: $ 20万
• 依托单位: Northern Arizona University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-15 至 2021-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2030488&HistoricalAwards=false
• 关键词: RAPID; Development; New; Test; SARS

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.

非技术描述：在新冠肺炎大流行期间，最具挑战性的方面之一是缺乏检测和跟踪感染的测试，以及缺乏谨慎地重新开放国家和经济活动的战略实施。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。这项工作是基于检测感染患者中病毒的非传统技术。该项目将基于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。这项技术将基于纳米技术和固体物理的最新发现，允许开发光谱技术来检测SARS-CoV-2病毒。这种名为单分子表面增强拉曼光谱(SM-SERS)的方法如果成功，将允许一种快速、廉价、更精确和可靠的方法来检测感染。该方法是基于对参与细胞感染的病毒S蛋白的检测。SM-SERS能够检测到一个分子的蛋白质，这将使感染得到早期检测，并对康复的患者进行随访。此外，对SM-SERS数据的进一步分析将有助于了解病毒蛋白质的变化，并有助于抗病毒药物的开发。技术描述：在新冠肺炎大流行期间，最具挑战性的方面之一是缺乏检测和跟踪感染的测试。检测试剂盒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。增加现有检测试剂盒数量的实际困难包括检测所需化学品的生产困难等。最常用的检测方法，在技术上被称为RT-qPCR，价格昂贵，周转时间长，尽管它高度敏感，但会产生许多假阴性，而且是基于生化方法。这项工作是基于其SM-SERS模式下的拉曼光谱。该方法是基于金属纳米颗粒上的局域表面等离子体对非弹性散射光的放大。主要目标将是建立SARS-CoV-2病毒刺突糖蛋白的拉曼特征，用于开发检测测试。PI小组以前的研究表明，基于唾液酸化糖蛋白分析的测试具有高敏感性、特异性和低假阴性率。该项目将开发一种新型的等离子纳米颗粒与离子液体相结合，将改善纳米颗粒对含有病毒的溶液的输送。第二个兴趣将是研究精细的峰结构，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。这项快速反应研究(RAPID)拨款支持的研究将开发一种新的病毒测试方法，资金来自CARE法案，该法案由数学和物理科学总监材料研究部的凝聚态物质物理计划管理。该奖项反映了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。