Diagnostic protein array for respiratory infections

呼吸道感染诊断蛋白阵列

• 批准号: 7324860
• 负责人: DARRELL P CHANDLER
• 金额: $ 29.45万
• 依托单位: AKONNI BIOSYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7324860
• 关键词: Adenoviruses; Antibiotics; Antibodies; Antigen Targeting; Area; Bacterial Infections; Clinic; Clinical; Collaborations; Detection; Development; Diagnosis; Diagnostic; Disease; Genus staphylococcus; Guidelines; Haemophilus influenzae; Hospitals; Human; Immunoassay; Individual; Influenza; Injection of therapeutic agent; Intellectual Property; Irrigation; Laboratories; Licensing; Logic; Longevity; Lung diseases; Medical Surveillance; Molds; Mycobacterium tuberculosis; Mycoplasma pneumoniae; Nose; Parainfluenza; Patients; Persons; Pharyngeal structure; Phase; Phosphate Buffer; Pneumonia; Preparation; Procedures; Process; Production; Protein Array; Public Health; Radiology Specialty; Reagent; Respiratory Tract Infections; SARS coronavirus; Saline; Sampling; Sputum; Streptococcus; Streptococcus Group B; Swab; Testing; Viral; Virus; base; cost; cross reactivity; detector; instrument; model development; pathogen; prototype; respiratory; respiratory protein; scale up; tool; user friendly software

DESCRIPTION (provided by applicant): The objective of this project is to transition Argonne-developed intellectual property into the commercial marketplace, and develop a protein array for clinical surveillance and diagnosis of common respiratory infections, including influenza A, influenza B, parainfluenza (types 1-3), human respiratory syncitial virus (RSV), adenovirus (types A-f), SARS coronavirus, group A Streptococcus, group B Streptococcus, Mycobacterium tuberculosis, Mycoplasma pneumonia, Haemophilus influenza, and Staphylococcus pneumoniae (12 pathogens). An array-based approach to respiratory disease diagnosis is recommended because it is difficult to differentiate between viral and bacterial infections based on clinical signs or radiology of the presenting patient, and because single-antibody tests are notoriously prone to false positives. A competitive immunoassay is proposed to militate against detector antibody cross-reactivity in a sandwich immunoassay array format; the sandwich immunoassay is reserved as a contingency to achieve the Phase 1 milestones. The decision logic and results from the protein array will enable public health officials to rapidly identify infected persons and intelligently administer costly and/or limited quantities of antibiotics or anti-viral therapies either in the clinic or in the field within 20 min of sample acquisition. We will meet these objectives by taking advantage of Akonni's exclusively-licensed intellectual property portfolio acquired from Argonne National Laboratory; proprietary antibodies, sample preparation reagents and know-how from Quidel Corporation; protein array expertise at Argonne National Laboratory; and clinical practice at Little Company of Mary Hospital. Specific Aims for the Phase 1 project are to: develop and implement a sample preparation and multiplexed immunoassay procedure within Akonni's fluidic development model sub-circuits; determine cross- reactivity of target antigens with Quidel antibodies in the competitive protein array; determine limits of detection and cross-reactivity for 12 individual pathogens in phosphate buffered saline and amended nasal swabs, lavage or sputum; and define process flow and instrument requirements for integrated fluidic cartridge development, production and testing in Phase 2. Successful completion of the project Milestones will provide sufficient justification to proceed with a Phase 2 proposal, where the Specific Aims will be to: integrate the sample preparation and protein array functions into a self-contained, integrated, injection-molded test cartridge; test and evaluate reagent stability and longevity within the test cartridge; encode the array decision logic into user-friendly software; test and evaluate the integrated prototype on neat and amended nasal swabs, throat swabs, nasal lavage and/or sputum clinical samples in accordance with 510K submission guidelines; and begin cartridge production scale-up in collaboration with Quidel. The Diagnostic Respiratory Protein Array test cartridge will represent a low-cost, simple diagnostic tool for identifying individuals infected with respiratory pathogens. The underlying platform developed herein will likewise find broad application in many areas of disease surveillance, with an emphasis on point-of-use applications.

描述（由申请人提供）：该项目的目的是将Argonne开发的知识产权转变为商业市场，并开发出一种蛋白质阵列，用于临床监测和常见呼吸道感染的临床监测和诊断，包括流感，流感，流感，parainfluenza（parainfluenza）冠状病毒，A组链球菌，B组链球菌，结核菌病，分枝杆菌肺炎，流感嗜血杆菌和肺炎葡萄球菌（12个病原体）。建议采用基于阵列的呼吸道疾病诊断方法，因为基于临床体征或放射学的患​​者很难区分病毒和细菌感染，并且由于众所周知，单抗体测试很容易发生假阳性。提出了一种竞争性免疫测定法，以在三明治免疫测定阵列格式中对检测器抗体交叉反应性进行反态。三明治免疫测定被保留为实现1阶段里程碑的偶然性。蛋白质阵列的决策逻辑和结果将使公共卫生官员能够快速识别感染者，并在诊所或样本习得的20分钟内智能地管理昂贵和/或有限数量的抗生素或抗病毒疗法。我们将利用Akonni独家获得的知识产权投资组合来实现这些目标； Quidel Corporation的专有抗体，样品制备试剂和专有技术； Argonne国家实验室的蛋白质阵列专业知识；和玛丽医院小公司的临床实践。第1阶段项目的具体目的是：在Akonni的流体发展模型子电路中开发和实施样品制备和多重免疫测定程序；确定靶抗原与竞争蛋白阵列中Quidel抗体的交叉反应性；确定在磷酸盐缓冲盐水中的12种单个病原体的检测和交叉反应限制，并修改了鼻拭子，灌洗或痰液；并在第2阶段定义了整合流体弹药型开发，生产和测试的过程流量和仪器要求。项目里程碑的成功完成将提供足够的合理性，以进行2阶段的提案，其中具体的目的将是：将样品制备和蛋白质阵列函数集成到一个自载，集成，注射，注射测试的弹药夹中；测试和评估试剂稳定性和寿命在测试弹药筒内；将数组决策逻辑编码到用户友好的软件中；根据510K提交指南，测试并评估并评估整洁和修订的鼻拭子，喉咙拭子，鼻腔灌洗和/或痰液临床样品的综合原型；并与Quidel合作开始墨盒生产规模。 诊断呼吸蛋白阵列测试弹药筒将代表一种低成本，简单的诊断工具，用于识别感染呼吸道病原体的个体。本文开发的基础平台同样将在许多疾病监测领域中找到广泛的应用，重点是使用点应用。