Rapid Clinical Surge-Testing for Biothreat Agents

描述(申请人提供)：在一次生物恐怖袭击后，数十万潜在受害者可能需要检测和治疗。对大量人进行接触生物制剂测试的迫切需要可能会使临床和公共卫生基础设施的能力不堪重负。实验室反应网络中负责协调准备和反应的大约25 000个哨兵实验室需要诊断工具，以便能够进行准确的分散检测。拟议项目的目标是为该网络开发一个浪涌测试平台。2001年的炭疽病袭击表明，对具有血液感染早期诊断证据的受害者进行积极治疗可以挽救生命。具体地说，我们将通过开发炭疽杆菌感染的血液测试来满足识别需要积极挽救生命的患者的需求，该测试使用我们在第一阶段演示的多路径(TM)测试系统来测试多种毒素和细胞抗原。多路径系统是理想的浪涌测试平台，具有超灵敏、定量、准确、成本效益、用户友好、便携和自动化的特点。该测试快速检测多个目标，灵敏度接近核酸扩增测试，但具有非处方药免疫分析“试条”测试的成本效益和用户友好性。在第一阶段，我们展示了多路径测试检测蛋白质、细菌和病毒靶标的水平比商业纸条测试低数千倍。这种灵敏度来自于使用一种专有的成像方法，该方法检测单个微粒，而不是在标准试条测试中检测信号所需的数百万个微粒。该系统将包括快速获取和自动检测血液样本的试剂盒(目标化验时间=5分钟)，以检测多种炭疽杆菌抗原的亚皮克水平(以将假阳性降至最低)；一个将患者与检测结果联系起来的识别系统；以及一个便携式独立近患者检测分析仪，它将自动处理批量加载的样本(每个样本10秒)，并将打印和无线发布结果。该应用程序的具体目标是(1)开发包含用于采集样本和自动运行化验的集成消耗品的原型消耗品试剂盒；(2)开发具有成本效益的批量加载的近患者分析仪；(3)集成系统组件；以及(4)展示该系统对全血样本中的炭疽杆菌灵敏和特异的检测效果。第二阶段的项目成果和交付成果将支持在公共卫生准备系统中实施多路径炭疽杆菌检测的第三阶段商业化目标。后续产品将包括对其他潜在生物制剂和感染剂的临床测试，以及在诊所外检测生物制剂的免仪器平台。多路径测试的竞争优势包括涵盖测试关键功能的知识产权、前所未有的高端结果和客户友好属性功能列表，以及直接的商业化路径。除了解决庞大且不断增长的生物恐怖主义市场外，多路径检测还可满足医疗保健(传染病、癌症、心血管疾病)和工业微生物学(食品、饮料、药品制造)领域尚未得到满足的重大检测需求。多路径测试将为一级和二级市场带来的价值应该会吸引大公司作为合作伙伴支持商业开发、营销和分销。

DESCRIPTION (provided by applicant): Following a bioterrorist attack, hundreds of thousands of potential victims may require testing and treatment. The critical need to test large numbers of people for exposure to a biothreat agent may overwhelm the capacity of the clinical and public health infrastructure. The approximately 25,000 sentinel laboratories in the Laboratory Response Network, which coordinates preparedness and response, need diagnostic tools to enable accurate decentralized testing. The goal of the proposed project is to develop a surge-testing platform for this network. The 2001 anthrax attacks showed that administering aggressive therapy to victims who have early diagnostic evidence of blood infections saves lives. Specifically, we will address the need for identifying patients that require aggressive life-saving therapy by developing a blood test for B. anthracis infection that tests for multiple-toxin and cellular antigens using the MultiPath(tm) testing system which we demonstrated in Phase I. The MultiPath system is an ideal surge-testing platform, being ultra-sensitive, quantitative, accurate, cost-effective, user-friendly, portable, and automated. The test rapidly detects multiple targets with sensitivities approaching nucleic acid amplification tests but with the cost-effectiveness and user-friendliness of over-the-counter immunoassay "strip" tests. In Phase I we showed that the MultiPath test detects protein, bacterial, and viral targets at levels up to thousands of times lower than commercial strip tests. This sensitivity comes from using a proprietary imaging approach which detects individual microparticles rather than the millions of particles required to detect a signal in standard strip tests. The system will comprise kits that acquire and automatically test blood samples rapidly (target assay time = 5 min) for sub-picogram levels of multiple B. anthracis antigens (to minimize false positives); an identification system to link patients to the test results; and a portable standalone near-patient test analyzer that will automatically process batch-loaded samples (<10 seconds per sample) and that will print and wirelessly post the results. The Specific Aims of the application are to (1) develop a prototype consumable kit containing an integrated consumable for collecting the sample and automatically running the assay; (2) develop the cost-effective batch-loadable near-patient analyzer; (3) integrate the system components; and (4) demonstrate the efficacy of the system to detect B. anthracis sensitively and specifically in whole blood samples. The Phase 2 project results and deliverables will support the Phase 3 commercialization goals for implementing the MultiPath B. anthracis test in the public health preparedness system. Follow-on products will include clinical tests for other potential biothreat and infectious agents and an instrument-free platform for detection of biothreat agents outside of the clinic. Competitive advantages of the MultiPath test include the intellectual property covering key features of the test, an unprecedented feature list of high-end results and customer-friendly attributes, and straightforward commercialization path. Besides addressing the large and growing bioterrorism market, the MultiPath test addresses significant unmet testing needs in healthcare (infectious disease, cancer, cardiovascular disease) and in industrial microbiology (food, beverage, pharmaceutical manufacturing). The value that the MultiPath test will bring to both the primary and secondary markets should attract large corporations as partners to support commercial development, marketing, and distribution.