Multiplexed POC Diagnostic System for Bio-Threat Agents

生物威胁因子多重 POC 诊断系统

• 批准号: 7009717
• 负责人: George B Sigal
• 金额: $ 430.96万
• 依托单位: MESO SCALE DIAGNOSTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7009717
• 关键词: Bacillus anthracis; Brucella; Coxiella burnetii; Francisella tularensis; Venezuelan equine encephalitis virus; Yersinia pestis; animal tissue; biohazard detection; biomedical equipment development; bioterrorism /chemical warfare; botulinum toxins; clinical biomedical equipment; clinical research; communicable disease diagnosis; cooperative study; diagnosis design /evaluation; human tissue; influenzavirus A; influenzavirus B; portable biomedical equipment; rapid diagnosis; respiratory syncytial virus; ricin; serology /serodiagnosis; staphylococcal enterotoxin; vaccinia virus

DESCRIPTION (provided by applicant): The development of a Multiplexed Point-of-Care Diagnostic System (MPDS) for rapid diagnosis of patients exposed to biological threat agents is proposed. The system will perform multiplexed measurements to allow for simultaneous detection and identification of multiple agents in both liquid (e.g., blood) and swab samples. Additional capabilities will include multiplexed serological testing of blood for antibody responses to threat agents. The proposed MPDS will consist of two elements: low cost, disposable cartridges and a small portable instrument for reading of cartridges. The disposable, single-use cartridges will contain all reagents necessary to conduct the assays and will use electrochemiluminescent detection. Two cartridge designs are proposed: one to measure analytes in liquid samples, including whole blood and plasma, and another to extract and measure analytes collected on swabs. The cartridges will be automatically processed and analyzed on a compact, portable instrument, providing results in less than 15 minutes. Specific goals of the program include: (1) refinement of MSD's cartridge and cartridge reader designs and demonstration of pilot scale production of both cartridges and reader; (2) development of multiplexed serology and direct detection assays for 10 biothreat agents; (3) transfer of the assay panels to the pilot cartridges and reader; (4) optimization of the assays on the cartridge platform in real matrices; and (5) extensive evaluation of assay performance. On successful completion of the proposed program, the system and assays will be developed to a level where they can subsequently be entered into pre-clinical and clinical validation studies. The proposed test panel for both antigen and serological tests include the following ten threat agents: Bacillus anthracis (BA), Yersinia pestis (YP), Francisella tularensis (FT), Coxiella burnetii (Q Fever), Brucellosis ssp, vaccinia virus, Venezuelan Equine Encephalitis (VEE), botulinum toxin A, ricin, and Staphylococcal enterotoxin B (SEB). In addition to these targets, the panel developed for swab samples will include assays for influenza A, influenza B, and RSV to identify patients whose symptoms are due to common respiratory ailments. Relevance: There is an urgent need for diagnostic systems capable of identifying biological threat agents and the diseases they cause. The proposed diagnostic system will fill that gap by providing rapid point-of-care diagnostics with the reliability and performance of the centralized laboratory. The system will be able to quickly identify individuals exposed to biological threat agents or their toxins, differentiate those individuals infected with common non-threat upper respiratory disease, and allow retrospective serological diagnosis to assist in epidemiological studies. The system is designed to be used by personnel without specialized training and will require no pre-processing of samples.

描述（由申请人提供）：建议开发多重护理点诊断系统（MPDS），用于对暴露于生物威胁剂的患者进行快速诊断。该系统将执行多重测量，以允许同时检测和识别液体（例如血液）和拭子样本中的多种试剂。其他功能将包括对血液进行多重血清学测试，以检测对威胁物质的抗体反应。拟议的 MPDS 将由两个要素组成：低成本、一次性墨盒和用于读取墨盒的小型便携式仪器。一次性的一次性试剂盒将包含进行测定所需的所有试剂，并将使用电化学发光检测。 提出了两种盒设计：一种用于测量液体样品中的分析物，包括全血和血浆，另一种用于提取和测量拭子上收集的分析物。墨盒将在紧凑的便携式仪器上自动处理和分析，并在 15 分钟内提供结果。该计划的具体目标包括： (1) 完善默沙东的卡式盒和卡式读卡器设计，并演示卡式盒和读卡器的中试规模生产； (2) 开发针对 10 种生物威胁因子的多重血清学和直接检测方法； (3) 将测定板转移至试验盒和读取器； (4) 实际基质中的试剂盒平台上的测定优化； (5) 分析性能的广泛评估。成功完成拟议项目后，系统和检测方法将开发到随后可以进入临床前和临床验证研究的水平。拟议的抗原和血清学测试组包括以下十种威胁病原体：炭疽杆菌 (BA)、鼠疫耶尔森菌 (YP)、土拉弗朗西斯菌 (FT)、伯内特柯克斯体 (Q 热)、布鲁氏菌病亚种、牛痘病毒、委内瑞拉马脑炎 (VEE)、肉毒杆菌毒素 A、蓖麻毒素和葡萄球菌肠毒素 B （SEB）。除了这些目标之外，为拭子样本开发的小组还将包括甲型流感、乙型流感和 RSV 检测，以识别其症状是由常见呼吸道疾病引起的患者。相关性：迫切需要能够识别生物威胁因子及其引起的疾病的诊断系统。拟议的诊断系统将通过提供快速的护理点诊断以及集中实验室的可靠性和性能来填补这一空白。该系统将能够快速识别暴露于生物威胁因子或其毒素的个体，区分那些感染常见非威胁性上呼吸道疾病的个体，并允许回顾性血清学诊断以协助流行病学研究。该系统设计为供未经专门培训的人员使用，并且无需对样品进行预处理。