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

基本信息

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
项目类别：
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

项目摘要

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）：最近发生的事件使开发可靠技术以快速、低水平检测 NIAID A 类优先病原体（A 类病原体）的需求达到了更加关键的水平。该项目将开发可部署的、基于纳米粒子的表面增强拉曼散射（SERS）诊断测试来满足这一需求。为此，该项目将重点关注三种血清标记物充分表征 A 类病原体（即炭疽杆菌、肉毒梭菌毒素和鼠疫耶尔森氏菌），基于选择性结合捕获的活性病原体抗原的外在拉曼标签 (ERL) 的超灵敏检测，设计并验证多重诊断面板的性能。 ERL 将使用独特的拉曼报告分子 (RRM) 和单克隆抗体 (mAb) 选择性地结合捕获的抗原，并产生显着增强的信号以进行超低水平检测。同时，我们还将设计和制造轻量级集成、封闭、从样本到答案平台的原型，该平台能够在被新型二极管激光器激发时从 ERL 读取特征 SERS 光谱。该平台可现场部署，具有桌面打印机大小的占地面积，并且 96 孔微孔板的读数约为 2 分钟。随着灭活病原体的测定在实验室中得到验证，程序将转移到 BSL-3 设施，在那里对活性 A 类病原体标记物的方法进行验证。当原型拉曼仪器和面板套件上市时，它们将在美国陆军杜格威试验场 (DPG) 的研究实验室（使用停用标记）和 BSL-3 设施（使用激活标记）进行 Beta 测试和性能验证）。该项目代表了犹他大学的科学家和工程师、B&W Tek, Inc.（拉曼光谱和相关自动化仪器的全球领导者）和 DPG 之间的合作关系。