Next Generation Plasmon Coupling Nanosensors

下一代等离子耦合纳米传感器

• 批准号: 2344525
• 负责人: Bjoern Reinhard
• 金额: $ 44.77万
• 依托单位: Trustees of Boston University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-03-01 至 2027-02-28
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2344525&HistoricalAwards=false
• 关键词: Next; Generation; Plasmon; Coupling; Nanosensors

Ribonucleic acid (RNA) molecules have diverse functions in controlling gene expression and controlling cellular behavior. RNA is also used by some viruses to store genetic information. These diverse and important functions motivate the development of sensors that allow for a sensitive detection and identification of RNA molecules. This project will develop RNA sensors for two specific classes of RNA molecules: i.) microRNA (miRNA), a regulatory class of RNA that has potential as biomarkers for diseases such as cancer, and ii.) viral RNA to enable a rapid detection of RNA viruses, such as the corona virus (Covid-19). The proposed sensor platform contains a DNA strand connected at its ends to two metal nanoparticles whose optical signal depend on their separation. The DNA sensor strand is designed to change its structure when it binds to a specific RNA target. This structural modification changes the separation between the nanoparticle probes and alters their signal, which is sensitively detected even for small nanoparticles via interference of the scattered signal with a reference light beam. The sensor will be designed to detect miRNA directly, but for viral RNA the coupled nanoparticle sensor will be combined with an enzymatic signal amplification step to obtain a sensitive and rapidly reconfigurable detection platform. The research will be integrated into education and outreach activities that include development of course work to support the research, organization of a summer workshop on the fundamentals of plasmonics and nanoscience for inner city high school students in the Boston area and their teachers that is designed to excite them about a career in science and technology, and development of an Instagram channel that will provide an excellent platform for educating a lay audience about plasmonic nanosensors.The project will combine molecular beacon like DNA structures whose ends are functionalized with noble metal nanoparticle (NP) probes with two-color interferometric scattering microscopy (iSCAT) detection to generate a plasmon coupling based sensor for two important classes of RNA: i.) regulatory miRNA and ii.) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA. Target RNA binding to the sensor induces a conformational change from a “closed” to an “open” conformation and alters the plasmon coupling between the NP labels bound to the DNA strand. Two-color iSCAT microscopy will be applied to enhance the sensitivity for detecting changes in the interferometric scattering signal associated with the opening of the sensor upon binding to its target. The DNA recognition element of the sensor will be designed to bind to miRNA directly, while for the viral RNA the plasmonic transducer will be combined with CRISPR-CAS13 detection and subsequent sample amplification to obtain a sensitive and reconfigurable viral RNA detection platform. Instead of directly binding to viral RNA, the molecular beacon will recognize RNA fragments generated through CAS13 trans-cleavage of a substrate.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.

核糖酸（RNA）分子在控制基因表达和控制细胞行为方面具有大型功能。某些病毒还使用RNA来存储遗传信息。这些潜水员和重要功能的传感器动机，允许对RNA分子进行敏感的检测和鉴定。该项目将为两种特定类别的RNA分子开发RNA传感器：i。）microRNA（miRNA），MicroRNA（miRNA）是一种有潜力作为癌症和II的生物标志物的RNA的调节类别。提出的传感器平台包含一个在其末端连接到两个金属纳米颗粒的DNA链，其光学信号取决于它们的分离。 DNA传感器链被设计为与特定RNA靶标结合时改变其结构。这种结构修饰会改变纳米颗粒问题之间的分离并改变其信号，即使对小纳米颗粒的敏感检测到通过参考光束的散射信号的干扰也被敏感地检测到。传感器将被设计为直接检测miRNA，但是对于病毒RNA，耦合的纳米颗粒传感器将与酶促信号放大步骤相结合，以获得敏感且快速重新配置的检测平台。这项研究将纳入教育和外展活动，包括开发课程，以支持研究，组织夏季研讨会，介绍有关波士顿内部城市高中生及其老师的基础知识和纳米科学的基础，旨在激发他们在Instagram频道中的职业和技术的发展，以使他们能够为莫尔的宗教提供良好的启示，以使他们能够跨越诺斯的望远平。像DNA结构一样，其末端用高贵的金属纳米颗粒（NP）具有两种彩色干涉散射显微镜（ISCAT）检测的问题，以生成基于等离子体的RNA的基于等离子体耦合的传感器：RNA：i。）调节性miRNA和II。靶RNA与传感器的结合诱导从“封闭”到“开放”构象的构象变化，并改变与DNA链结合的NP标签之间的等离子体耦合。将应用两色ISCAT显微镜，以增强检测与传感器与其靶标结合后与传感器打开相关的干涉散射信号变化的灵敏度。传感器的DNA识别元件将被设计为直接与miRNA结合，而对于病毒RNA，等离子传感器将与CRISPR-CAS13检测和随后的样品放大结合，以获得敏感且可重新配置的病毒RNA检测平台。分子信标未直接与病毒RNA结合，而是识别通过CAS13的底物产生的RNA片段。该奖项反映了NSF的法定任务，并被认为是通过基金会的智力优点和更广泛影响标准的智力优点评估而被视为珍贵的支持。