Rapid, accurate and user-friendly clinical surge-testing for biothreat agents

描述(申请人提供)：在发生重大生物恐怖主义袭击或传染病爆发后，数百万潜在受害者可能需要快速检测，以确保向需要治疗的人提供挽救生命的治疗。由于今天没有能够在危机情况下进行高性能大规模测试的诊断方法，数千人可能会由于宝贵医疗资源的低效定向而不必要地死亡。我们正在开发多路径TM浪涌测试平台，这是第一个专为现场临床浪涌测试设计的高性能高通量系统。该系统具有快速、高通量、灵敏、定量、准确、性价比高、界面友好、便携、自动化等特点，是一种理想的浪涌测试平台。它可以对广泛的生物制剂或传染病病原体进行测试，包括细菌、真菌、病毒和毒素。虽然与高性能中央实验室测试一样灵敏，但多路径分析与非处方快速测试一样快速和易于使用，并且不需要样品准备。专有的多路径免疫分析技术通过使用数字成像来计算标记有荧光颗粒的目标分子而不使用放大倍数，从而实现了高灵敏度和量化。多路径分析设计消除了洗涤步骤，降低了工程复杂性和成本，同时提高了产量。在二期SBIR的基础上，设计并集成了功能齐全的多路浪涌试验平台原型和灵敏的炭疽浪涌试验样机。我们的数据表明，多路炭疽试验快速(6min)和灵敏(低pg/ml)检测两个炭疽标志物具有高准确性(每个标志物包括内阳性和阴性对照试验)和特异性，在小的全血指棒样本中不需要样品准备。原型多路径平台自动执行600次/小时的分析，并集成了自动液体处理、样品跟踪、数据分析和报告生成。我们建议开发商用多路浪涌测试平台和多路炭疽试验。具体地说，我们建议(1)开发用于超灵敏多路径炭疽测试的商用质量颗粒免疫试剂，(2)开发可在室温下长期储存的大规模生产试剂的制造工艺，(3)开发商业多路径浪涌测试平台，(4)集成多路径浪涌测试平台和多路径炭疽测试，以及(5)验证平台和炭疽测试的有效性。为了补充我们在开发多路径平台和检测方面的核心专业知识，我们将利用学术、行业和政府合作者的专业知识。在拟议的项目完成后，我们将开始验证平台和炭疽测试，以便随后提交监管机构。我们建议部署浪涌测试平台和试剂，以在公共卫生系统的关键地点--包括国家战略储备、州和市公共卫生机构以及实验室反应网络--测试生物制剂和疾病暴发制剂的菜单。公共卫生相关性：在发生重大生物恐怖主义袭击或传染病暴发后，数百万潜在受害者可能需要快速有效的检测，以确保向需要治疗的人提供挽救生命的治疗。由于今天没有能够在危机情况下进行高性能大规模测试的诊断方法，数千人可能会由于宝贵医疗资源的低效定向而不必要地死亡。为了解决国家公共卫生准备大规模浪涌试验的严重差距，我们建议开发多路径浪涌试验平台和多路径炭疽试验。

DESCRIPTION (provided by applicant): Following a major bioterrorism attack or infectious disease outbreak, millions of potential victims may require rapid testing to ensure delivery of life-saving therapeutic treatment to those who need it. Because today there is no diagnostic method capable of high-performance large-scale testing in a crisis situation, thousands could die needlessly due to inefficient targeting of precious medical resources. We are developing the MultiPathTM Surge Testing Platform, the first high-performance high-throughput system designed for on-site clinical surge testing. The MultiPath system is an ideal surge-testing platform, being rapid, high throughput, sensitive, quantitative, accurate, cost-effective, user-friendly, portable, and automated. It accommodates tests for a broad menu of biothreat or infectious disease agents including bacteria, fungi, viruses, and toxins. While as sensitive as high performance central laboratory tests, the MultiPath assays are as rapid and as easy-to-use as over-the-counter rapid tests and require no sample preparation. The proprietary MultiPath immunoassay technology achieves high sensitivity and quantification by using digital imaging to count target molecules tagged with fluorescent particles without using magnification. The MultiPath assay design eliminates wash steps, reducing engineering complexity and cost while increasing throughput. Under a Phase II SBIR we designed and integrated a fully functional prototype of the MultiPath Surge Testing Platform and a sensitive surge test for anthrax. Our data demonstrate that the MultiPath Anthrax test rapidly (6 min) and sensitively (low pg/ml) detects two anthrax markers with high accuracy (internal positive and negative control assays are included for each marker) and specificity in small whole blood fingerstick samples with no sample prep. The prototype MultiPath platform automatically performs 600 assays/hour and integrates automated liquid handling, sample tracking, data analysis, and report generation. We propose to develop the commercial MultiPath Surge Testing Platform and MultiPath Anthrax Test. Specifically, we propose to (1) develop commercial quality particle-based immunoreagents for the ultra-sensitive MultiPath Anthrax test, (2) develop manufacturing procedures for large scale production of reagents that can be stored long-term at room temperature, (3) develop the commercial MultiPath Surge Testing Platform, (4) integrate the MultiPath Surge Testing Platform and MultiPath Anthrax test, and (5) verify the efficacy of the platform and anthrax test. To supplement our core expertise in developing MultiPath platform and assays, we will leverage the expertise of academic, industry, and government collaborators. On completion of the proposed project we will begin validation of the platform and anthrax test for subsequent regulatory submission. We propose to deploy the surge-testing platform and reagents to test for a menu of biothreat and disease outbreak agents at key points in the public health system - including the Strategic National Stockpile, state and city public health institutions, and the Laboratory Response Network. PUBLIC HEALTH RELEVANCE: Following a major bioterrorism attack or infectious disease outbreak, millions of potential victims may require rapid and efficient testing to ensure delivery of life-saving therapeutic treatment to those who need it. Because today there is no diagnostic method capable of high-performance large-scale testing in a crisis situation, thousands could die needlessly due to inefficient targeting of precious medical resources. To address the critical gap in the nation's public health preparedness for large-scale surge testing we propose to develop the MultiPath Surge Testing Platform and the MultiPath Anthrax Test.