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

• 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
• 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

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）： 在接下来的十年中，有很大的可能性要么会出现流感（流感）大流行，这是一种新型呼吸道病毒（RV）的主要流行病[例如，SARS]，或者是生物恐怖主义攻击，导致呼吸道症状。此外，每年多达500,000人死亡，并且没有方法可以将流感与许多其他常见的RV感染区分开。迫切需要敏感，高度廉价，便携式，低复杂性设备/测定法，以允许对流感和其他常见RV的多重检测和鉴定。我们在开发流感和其他RVS的多重商业测定方面有很长的记录，并开发了世界上第一个用于流感A，B，RSV A，B和Parainflu 1,2,3的商业多重分子​​测定法（Hexaplex，1996）和SARS的第一个测定法（2003年）。现在，我们已经基于独特的样品收集装置（SCD），稳定的欧洲荧光微粒（EFM）和基于PRNA的结合化学开发了新颖的完全集成技术，该技术允许敏感（400X> 400x> bact anf FDA批准的测定）或现场内部或现场内部多重POC POC POC POC POC抗原测试患者的患者。该技术在电池上运行，需要15分钟，并且可以同时检测多个病毒。更重要的是，SCD收集并稳定核酸样品（RNA和DNA），以根据需要在分子测定中使用（允许测试阴性样品或在维持生物培养的同时进一步分析阳性）。在此应用程序中，我们提出以下特定目标：！ 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。将多重RT-PCR电子微阵列（EMR）测定与这些13个病毒与确认性分子测定（也是产品），确定和比较分析LOD，灵敏度和特异性与在SA 1和其他已建立的分子测定中开发的多重免疫测定法。 3。确定FDA所需的最佳参数。 （例如，确保设计所有组件，易用性指南以及非专业实验室人员的结果解释，符合CLIA在SA＃1中放弃测定的标准）； 4。过程开发（以合理的成本确保诊断组件和商业化的生产性的方法）。 5。临床样品测试（冷冻样品）；为了确定SA＃1和2中的多重POC分析是否针对大多数RV产生“流感样”症状和LRI是否可以证明与当前可用的标准诊断测定相比，可以证明临床敏感性，特异性和成本效益提高。这些SAS完成后，临床医生和公共卫生官员将有两种重要的新工具来抗击流感和病毒呼吸道感染，无论是从其医院，办公室还是地球上最偏远的地方。