Surface-enhanced Raman Spectroscopy Immunoassay for Detection of Category A Patho

用于检测 A 类病理的表面增强拉曼光谱免疫分析

• 批准号: 9278001
• 负责人: Marc D Porter
• 金额: $ 61.58万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9278001
• 关键词: Anthrax disease; Antigens; Applications Grants; Arts; Bacillus anthracis; Binding; Biological; Biological Assay; Biological Warfare; Botulinum Toxins; Botulism; Categories; Certification; Characteristics; Chemicals; Chemistry; Clinical; Communication; Containment; Country; Data Analyses; Detection; Development; Diagnostic; Diagnostic Sensitivity; Diagnostic Specificity; Diagnostic tests; Disease; Engineering; Equipment; Event; FDA approved; Fiber Optics; Goals; Gold; Human Resources; Immunoassay; Immunological Diagnosis; In Vitro; Label; Laboratories; Laboratory Procedures; Laboratory Research; Lasers; Legal patent; Liquid substance; Measurement; Medical Device; Methods; Monoclonal Antibodies; National Institute of Allergy and Infectious Disease; Pathology; Pathway interactions; Performance; Phase; Plague; Preparation; Probability; Process; Public Health; Raman Spectrum Analysis; Reading; Recombinants; Recording of previous events; Reporter; Resource Development; Safety; Sampling; Scientist; Security; Series; Serum; Serum Markers; Signal Transduction; Source; Specificity; Speed; Surface; System; Technology; Testing; Training; Universities; Utah; Validation; Virus; Wireless Technology; Work; Yersinia pestis; active method; base; biodefense; biosafety level 3 facility; botulinum; combat; cost; cost effectiveness; design; diagnostic biomarker; diagnostic panel; experience; improved; innovation; instrument; instrumentation; light weight; medical schools; microorganism toxin; monolayer; multiplex detection; nanoparticle; particle; pathogen; pathogen exposure; portability; prototype; public health emergency; public health relevance; rapid detection; rapid technique; surfactant; technique development; therapeutic development; tool; vaccine development; weapons of mass destruction

DESCRIPTION (provided by applicant): Recent events have placed the need for the development of reliable techniques for the rapid, low-level detection of NIAID Category A Priority Pathogens (Category A Pathogens) at an even more critical level. This project will develop deployable, nanoparticle-based, surface enhanced Raman scattering (SERS) diagnostic tests to fill this need. In so doing, this project will focus on serum markers for three well characterized Category A Pathogens (i.e., Bacillus anthracis, Clostridium botulinum toxin, and Yersinia pestis) in devising and performance-validating a multiplexed diagnostic panel based on the ultrasensitive detection of extrinsic Raman labels (ERLs) selectively bound to captured active pathogen antigens. ERLs will use unique Raman reporter molecules (RRMs) and monoclonal antibodies (mAbs) to selectively bind to captured antigens and to generate a markedly enhanced signal for ultra-low-level detection. Concurrently, we will also design and manufacture prototypes of a lightweight integrated, closed, sample-to-answer platform capable of reading the characteristic SERS spectrum from the ERLs when excited by a new diode laser. The platform will be field-deployable, have a desktop printer-size footprint, and have a readout of ~2 min for a 96-well microplate. As assays for the deactivated pathogens are validated in the laboratory the procedures will be transferred into a BSL-3 facility where methods for the active Category A Pathogen markers will be validated. When the prototypic Raman instruments and panel kits are available, they will be beta-tested and performance validated in the research laboratory (with deactivated markers) and in the BSL-3 facility (with active markers) at the U.S. Army's Dugway Proving Ground (DPG). This project represents a partnership between scientists and engineers at the University of Utah, B&W Tek, Inc. (a global leader in Raman spectroscopy and related automated instrumentation), and DPG.

描述（由申请人提供）：最近的事件使得开发可靠技术，以在更关键的水平上快速，低级检测A的NIAID类别A优先病原体（A类病原体）。该项目将开发可部署的，基于纳米颗粒的，表面增强的拉曼散射（SERS）诊断测试，以满足这一需求。这样做，这个项目将重点放在三个的血清标记上 具有良好特征的类别A病原体（即炭疽芽孢杆菌，肉毒杆菌毒素和鼠疫耶尔森乳梭状芽胞杆菌）在设计和性能验证基于超级敏感性的散发性拉曼Labels（ERL）的超敏感性检测中，选择性地结合到捕获的活性病原体抗生素。 ERL将使用独特的拉曼记者分子（RRMS）和单克隆抗体（mAb）选择性结合与捕获的抗原，并产生明显增强的信号，以实现超低水平检测。同时，我们还将设计和制造轻巧的集成，封闭式，样品对撤离平台的原型，该平台能够通过新的二极管激光兴奋时从ERL中读取特征性的SERS频谱。该平台将是可登机的，具有桌面打印机大小的占地面积，并在96孔微孔板上读数约2分钟。由于在实验室中验证了停用病原体的测定，因此将将程序转移到BSL-3设施中，其中有效类别的方法将验证病原体标记物。当可用原型拉曼仪器和面板套件时，将经过β测试并在研究实验室（带有停用标记）以及在美国陆军的Dugway Proving Groud（DPG）的BSL-3设施（带有主动标记）中进行了验证。该项目代表了犹他大学，B＆W Tek，Inc。（拉曼光谱和相关自动化仪器的全球领导者）和DPG之间的科学家与工程师之间的合作伙伴关系。