Multipled POC device for antigen/molecular detection of influenza & other viruses

用于流感抗原/分子检测的多重POC装置

基本信息

批准号：
7452634
负责人：
Kelly J. Henrickson
金额：
$ 50万
依托单位：
MEDICAL COLLEGE OF WISCONSIN
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-07-08 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7452634
关键词：
Acute Adenoviruses Adult Anthrax Attack Anthrax disease Antigenic Variation Antigens Arts Aspirate substance Avian Influenza Back Bacteria Bedside Testings Binding Bioinformatics Biological Biological Assay Bioterrorism Canada Categories Centers for Disease Control and Prevention (U.S.)Chemistry Child Clinical Clinical Research Clinical Sensitivity Communicable Diseases Communities Community-Acquired Infections Coronavirus Cost Analysis Cyclic GMP DNA Detection Developed Countries Developing Countries Development Devices Diagnosis Diagnostic Disease Documentation Drug Formulations Electronics Emerging Communicable Diseases Engineering Ensure Enterovirus Enzyme-Linked Immunosorbent Assay Epidemic Europium Event Freezing Future Genes Genome Goals Gold Guidelines H7N7 Hospitals Human Immunoassay Indium Influenza Influenza A Virus, H5N1 Subtype Informed Consent International Cooperation Knowledge Laboratories Laboratory Personnel Lateral Legal patent Length Location Lung diseases Manufacturer Name Marketing Medical Surveillance Methods Molecular Molecular Diagnosis Monoclonal Antibodies Mutate Myocardial Infarction National Institute of Allergy and Infectious Disease New Agents Nose Nucleic Acids Nucleoproteins Numbers Operative Surgical Procedures Patients Performance Pharyngeal structure Phase Physicians Placement Planets Pliability Pneumonia Polymerase Chain Reaction Principal Investigator Probability Process Production Public Health RNA RNA Viruses Range Reading Reagent Recording of previous events Research Research Ethics Committees Research Personnel Research Project Grants Respiratory Tract Infections Role Running Sampling Scientist Screening procedure Sensitivity and Specificity Sepsis Severe Acute Respiratory Syndrome Shoulder Source Specificity Specimen Speed Standards of Weights and Measures Statistically Significant Structural Protein Swab Symptoms System Techniques Technology Test Result Testing Time United States United States Food and Drug Administration United States National Institutes of Health Update Validation Viral Virulent Virus Virus Diseases Whole Organism Work base commercialization cost cost effectiveness demographics design epizootic expectation experience fighting flu improved influenzavirus internal control killings method development multiplex detection novel nucleic acid detection pandemic disease pandemic influenza pathogen point of care preclinical study programs prototype rapid diagnosis research study respiratory respiratory infection virus respiratory virus sample collection tool

项目摘要

DESCRIPTION (provided by applicant): There is a significant probability that in the next decade there will be either an influenza (flu) pandemic, a major epidemic of a novel respiratory virus (RV) [e.g., SARS], or a bioterrorism attack that results in respiratory symptoms. In addition, as many as 500,000 people die each year of flu and there is no method to clinically distinguish flu from the many other common RV infections. There is an urgent need for sensitive, highly specific, inexpensive, portable, low complexity devices/assays that allow for the multiplex detection and identification of flu and other common RV's. We have a long record of developing multiplex commercial assays for flu and other RVs and developed the first commercial multiplex molecular assay for flu A, B, RSV A, B, and parainflu 1,2,3 in the world (Hexaplex, 1996) and the first assay for SARS in the US (2003). We have now developed novel fully integrated technology based on a unique sample collection device (SCD), stable europium fluorescent microparticles (EFM), and binding chemistry based on pRNA that allows for sensitive (400x > than FDA approved assays) bedside or in-the-field multiplex POC antigen testing of patients. This technology runs on batteries, takes 15 minutes, and can detect multiple viruses simultaneously. Even more importantly the SCD collects and stabilizes a sample of nucleic acid (RNA and DNA) for use in molecular assays as needed (allowing for testing of negative samples or further analysis of positives while maintaining biocontainment). In this application we propose the following specific aims:! Select and optimize the chemistry, substrate, and hardware to produce a SCD-EFM-pRNA assay to detect 13 common RV's causing LRI or significant disease in children and adults (flu A, B, RSV, [paraflu 1,2,3, hMPV], corona- viruses [NL63, HKU1, 229E, OC43], adenovirus, and enterovirus). 2. Develop a multiplex-RT-PCR electronic microarray (eMR) assay to these same 13 viruses as a confirmatory molecular assay (also as a product), determine and compare analytical LOD, sensitivity and specificity with multiplex immunoassay developed in SA 1 and other established molecular assays. 3. Determine optimal parameters required by FDA. (e.g., ensure design of all components, ease of use guidelines, and results interpretation by non-professional laboratory personnel meets CLIA waived standards for assay in SA#1); 4. Process Development (methods to ensure manufacturability of the diagnostic components and commercialization at a reasonable cost). 5. Clinical sample testing (frozen samples); To determine if the multiplex POC assays developed in SA#1 & 2 to the majority of RV that produce "Flu-like" symptoms and LRI can demonstrate improved clinical sensitivity, specificity, and cost effectiveness compared to currently available standard diagnostic assays. After completion of these SAs, clinicians and public health officials will have two important new tools to fight flu and viral respiratory infections, whether from their hospital, office or the most remote locations on the planet.

描述（由申请人提供）：未来十年很可能会发生流感（流感）大流行、新型呼吸道病毒（RV）[例如SARS]的大流行，或导致呼吸道症状的生物恐怖袭击。此外，每年有多达 50 万人死于流感，并且临床上没有方法将流感与许多其他常见的 RV 感染区分开来。迫切需要灵敏、高度特异性、廉价、便携式、低复杂性的设备/测定法，以允许对流感和其他常见 RV 进行多重检测和识别。我们在开发针对流感和其他 RV 的多重商业检测方法方面拥有悠久的记录，并开发了世界上第一个针对流感 A、B、RSV A、B 和副流感 1、2、3 的商业多重分子检测方法（Hexaplex，1996 年）和美国首次检测 SARS（2003 年）。我们现已开发出新颖的完全集成技术，基于独特的样品收集装置 (SCD)、稳定的铕荧光微粒 (EFM) 和基于 pRNA 的结合化学，可实现灵敏（比 FDA 批准的检测高 400 倍）床边或体内-对患者进行现场多重POC抗原检测。该技术依靠电池运行，需要 15 分钟，可以同时检测多种病毒。更重要的是，SCD 收集并稳定核酸（RNA 和 DNA）样本，以便根据需要用于分子测定（允许测试阴性样本或进一步分析阳性样本，同时保持生物防护）。在此应用中，我们提出以下具体目标：！选择并优化化学物质、底物和硬件，以生成 SCD-EFM-pRNA 检测，以检测 13 种常见 RV 引起的 LRI 或儿童和成人的重大疾病（流感 A、B、RSV、[paraflu 1,2,3、hMPV] ]、冠状病毒[NL63、HKU1、229E、OC43]、腺病毒和肠道病毒）。 2. 开发针对这 13 种病毒的多重 RT-PCR 电子微阵列 (eMR) 测定作为确证性分子测定（也作为产品），确定分析 LOD、灵敏度和特异性，并与 SA 1 和其他开发的多重免疫测定进行比较建立了分子测定。 3. 确定 FDA 要求的最佳参数。（例如，确保所有组件的设计、易用性指南以及非专业实验室人员的结果解释符合 SA#1 中的 CLIA 豁免测定标准）； 4.工艺开发（确保诊断组件的可制造性和以合理成本商业化的方法）。 5.临床样本检测（冷冻样本）；确定 SA#1 和 2 中开发的针对大多数产生“流感样”症状和 LRI 的 RV 的多重 POC 检测是否可以证明与目前可用的标准诊断检测相比，临床敏感性、特异性和成本效益有所提高。完成这些 SA 后，临床医生和公共卫生官员将拥有两种重要的新工具来对抗流感和病毒性呼吸道感染，无论是在医院、办公室还是地球上最偏远的地方。